A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.
A sterol regulatory element binding protein that regulates GENES involved in CHOLESTEROL synthesis and uptake.
Sterol regulatory element binding proteins are basic helix-loop-helix leucine zipper transcription factors that bind the sterol regulatory element TCACNCCAC. They are synthesized as precursors that are threaded into the MEMBRANES of the ENDOPLASMIC RETICULUM.
A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.
Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
De novo fat synthesis in the body. This includes the synthetic processes of FATTY ACIDS and subsequent TRIGLYCERIDES in the LIVER and the ADIPOSE TISSUE. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.
Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.
An enzyme that catalyzes the synthesis of hydroxymethylglutaryl-CoA from acetyl-CoA and acetoacetyl-CoA. This is a key enzyme in steroid biosynthesis. This enzyme was formerly listed as EC 4.1.3.5.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A form species of spore-producing CYANOBACTERIA, in the family Nostocaceae, order Nostocales. It is an important source of fixed NITROGEN in nutrient-depleted soils. When wet, it appears as a jelly-like mass.
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An enzyme involved in the MEVALONATE pathway, it catalyses the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate.
An enzyme that catalyzes the formation of oleoyl-CoA, A, and water from stearoyl-CoA, AH2, and oxygen where AH2 is an unspecified hydrogen donor.
DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.
Cholesterol which is substituted by a hydroxy group in any position.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.
A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.
Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Established cell cultures that have the potential to propagate indefinitely.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Animal form of fatty acid synthase which is encoded by a single gene and consists of seven catalytic domains and is functional as a homodimer. It is overexpressed in some NEOPLASMS and is a target in humans of some ANTINEOPLASTIC AGENTS and some ANTI-OBESITY AGENTS.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Triglycerides are the most common type of fat in the body, stored in fat cells and used as energy; they are measured in blood tests to assess heart disease risk, with high levels often resulting from dietary habits, obesity, physical inactivity, smoking, and alcohol consumption.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Nucleic acid sequences involved in regulating the expression of genes.
Fluorinated hydrocarbons are organic compounds consisting primarily of carbon and fluorine atoms, where hydrogen atoms may also be present, known for their high stability, chemical resistance, and various industrial applications, including refrigerants, fire extinguishing agents, and electrical insulation materials.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
The processes whereby the internal environment of an organism tends to remain balanced and stable.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Transport proteins that carry specific substances in the blood or across cell membranes.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Proteins prepared by recombinant DNA technology.
An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.
Substances used to lower plasma CHOLESTEROL levels.
Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.
A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Regular course of eating and drinking adopted by a person or animal.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.

YY1 is a negative regulator of transcription of three sterol regulatory element-binding protein-responsive genes. (1/334)

Ying Yang 1 (YY1) is shown to bind to the proximal promoters of the genes encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, farnesyl diphosphate (FPP) synthase, and the low density lipoprotein (LDL) receptor. To investigate the potential effect of YY1 on the expression of SREBP-responsive genes, HepG2 cells were transiently transfected with luciferase reporter constructs under the control of promoters derived from either HMG-CoA synthase, FPP synthase, or the LDL receptor genes. The luciferase activity of each construct increased when HepG2 cells were incubated in lipid-depleted media or when the cells were cotransfected with a plasmid encoding mature sterol regulatory element-binding protein (SREBP)-1a. In each case, the increase in luciferase activity was attenuated by coexpression of wild-type YY1 but not by coexpression of mutant YY1 proteins that are known to be defective in either DNA binding or in modulating transcription of other known YY1-responsive genes. In contrast, incubation of cells in lipid-depleted media resulted in induction of an HMG-CoA reductase promoter-luciferase construct by a process that was unaffected by coexpression of wild-type YY1. Electromobility shift assays were used to demonstrate that the proximal promoters of the HMG-CoA synthase, FPP synthase, and the LDL receptor contain YY1 binding sites and that YY1 displaced nuclear factor Y from the promoter of the HMG-CoA synthase gene. We conclude that YY1 inhibits the transcription of specific SREBP-dependent genes and that, in the case of the HMG-CoA synthase gene, this involves displacement of nuclear factor Y from the promoter. We hypothesize that YY1 plays a regulatory role in the transcriptional regulation of specific SREBP-responsive genes.  (+info)

Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1. (2/334)

Cholesteryl ester transfer protein (CETP) is expressed in human adipocytes, where it acts to promote selective uptake of HDL-CE (Benoist, F., M. McDonnell, P. Lau, R. Milne, and R. McPherson. 1997. J. Biol. Chem. 272: 23572;-23577). In contrast to other major sterol-responsive genes such as 3-hydroxy-3-methylglutaryl coenzyme A reductase CETP expression is up-regulated rather than down-regulated in response to cholesterol. To define elements involved in cholesterol-mediated up-regulation of CETP gene expression, deletion derivatives of the CETP promoter were cloned into a luciferase reporter construct and transfected into the human liposarcoma cell line SW872, cultured in the presence or absence of lipoproteins. A fragment associated with a positive cholesterol response was identified between nucleotides -361 and -138 (relative to the initiation site of transcription) of the promoter. This region contains a tandem repeat of a sequence known to mediate sterol dependent regulation of the hamster HMG-CoA reductase gene. We have putatively denoted this region, the cholesterol response element (CRE). Using gel mobility shift assays we demonstrate that both YY1 and SREBP-1 interact with the CRE of CETP. Furthermore, in transient co-transfection experiments, both YY1 and SREBP-1a were found to trans-activate, in a dose-dependent manner, the luciferase activity of constructs harboring the CRE. We also demonstrate that SREBP-2, is able to trans-activate a luciferase construct harboring the CRE although much less effectively as compared to SREBP-1. Finally, functional analysis of the CRE confirms its regulatory role in modulating CETP gene expression through its interaction with YY1 and SREBP-1a.  (+info)

Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip. (3/334)

The sterol regulatory element-binding protein-2 (SREBP-2) is produced as a large precursor molecule attached to the endoplasmic reticulum membrane. In response to the sterol depletion, the N-terminal segment of the precursor, which contains a basic helix-loop-helix-leucine zipper domain, is released by two sequential cleavages and is translocated to the nucleus, where it activates the transcription of target genes. The data herein show that released SREBP-2 uses a distinct nuclear transport pathway, which is mediated by importin beta. The mature form of SREBP-2 is actively transported into the nucleus when injected into the cell cytoplasm. SREBP-2 binds directly to importin beta in the absence of importin alpha. Ran-GTP but not Ran-GDP causes the dissociation of the SREBP-2-importin beta complex. G19VRan-GTP inhibits the nuclear import of SREBP-2 in living cells. In the permeabilized cell in vitro transport system, nuclear import of SREBP-2 is reconstituted only by importin beta in conjunction with Ran and its interacting protein p10/NTF2. We further demonstrate that the helix-loop-helix-leucine zipper motif of SREBP-2 contains a novel type of nuclear localization signal, which binds directly to importin beta.  (+info)

Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins. (4/334)

Site-1 protease (S1P) is a subtilisin-related protease that cleaves sterol regulatory element-binding proteins (SREBPs) in the endoplasmic reticulum lumen, thereby initiating a process by which the transcriptionally active NH(2)-terminal fragments of SREBPs are released from membranes. In the current experiments, we transfected cDNAs encoding epitope-tagged hamster S1P into HEK-293 cells or mutant hamster cells that lack S1P. Protease protection assays showed that the bulk of S1P is in the endoplasmic reticulum lumen, anchored by a COOH-terminal membrane-spanning segment. Cleavage of the NH(2)-terminal signal sequence of S1P generates S1P-A (amino acids 23-1052), which is inactive. The protein is self-activated by an intramolecular cleavage at Site-B, generating S1P-B (amino acids 138-1052) and liberating a 115-amino acid propeptide that is secreted intact into the medium. The sequence at Site-B is RSLK, which differs from the RSVL sequence at the cleavage site in SREBP-2. S1P-B is further cleaved at an internal RRLL sequence to yield S1P-C (amino acids 187-1052). Mutational analysis suggests that S1P-B and S1P-C are both active in cleaving SREBP-2 in a fashion that requires SREBP cleavage-activating protein. The activity of S1P-C may be short-lived because it appears to be transported to the Golgi, a site at which SREBP-2 cleavage may not normally occur. These data provide the initial description of the processing of a subtilisin-related protease that controls the level of cholesterol in blood and cells. In an accompanying paper (Cheng, D., Espenshade, P. J., Slaughter, C. A., Jaen, J. C., Brown, M. S., and Goldstein, J. L. (1999), J. Biol. Chem., 274, 22805-22812), we develop an in vitro assay to characterize the activity of purified recombinant S1P.  (+info)

Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins. (5/334)

We describe a permanent line of Chinese hamster ovary cells transfected with a cDNA encoding a truncated form of Site-1 protease (S1P) that is secreted into the culture medium in an enzymatically active form. S1P, a subtilisin-like protease, normally cleaves the luminal loop of sterol regulatory element-binding proteins (SREBPs). This cleavage initiates the two-step proteolytic process by which the NH(2)-terminal domains of SREBPs are released from cell membranes for translocation to the nucleus, where they activate transcription of genes involved in the biosynthesis and uptake of cholesterol and fatty acids. Truncated S1P (amino acids 1-983), produced by the transfected Chinese hamster ovary cells, lacks the COOH-terminal membrane anchor. Like native S1P, this truncated protein undergoes normal autocatalytic processing after residue 137 to release an NH(2)-terminal propeptide, thereby generating an active form, designated S1P-B. Prior to secretion, truncated S1P-B, like native S1P-B, is cleaved further after residue 186 to generate S1P-C, which is the only form that appears in the culture medium. The secreted enzyme, designated S1P(983)-C, cleaves a synthetic peptide that terminates in a 7-amino-4-methyl-coumarin fluorochrome. This peptide, RSLK-MCA, corresponds to the internal propeptide cleavage site that generates S1P-B as described in the accompanying paper (Espenshade, P. J., Cheng, D., Goldstein, J. L., and Brown, M. S. (1999), J. Biol. Chem. 274, 22795-22804). The secreted enzyme does not cleave RSVL-MCA, a peptide corresponding to the physiologic cleavage site in SREBP-2. However, S1P(983)-C does cleave after this leucine when the RSVL sequence is contained within a 16-residue peptide corresponding to the central portion of the SREBP-2 luminal loop. The catalytic activity of S1P(983)-C differs from that of furin/prohormone convertases, two related proteases, in its more alkaline pH optimum (pH 7-8), its relative resistance to calcium chelating agents, and its ability to cleave after lysine or leucine rather than arginine. These data provide direct biochemical evidence that S1P is the protease that cleaves SREBPs and thereby functions to control lipid biosynthesis and uptake in animal cells.  (+info)

Sterol regulatory element-binding protein negatively regulates microsomal triglyceride transfer protein gene transcription. (6/334)

We herein report that mRNA expression of microsomal triglyceride transfer protein (MTP) and its protein synthesis decline in response to sterol depletion in HepG2 cells, and we functionally characterized the MTP gene promoter in an effort to investigate the molecular mechanisms by which MTP gene transcription is regulated. Luciferase assays using truncated versions of the reporter gene revealed that the region at -124 to +33 base pairs of the human promoter contains the elements required for the suppression of transcription by sterol depletion. Enforced expression of an active form of sterol regulatory element-binding protein (SREBP)-1 (amino acids 1-487) or -2 (amino acids 1-481), both of which are activated under sterol-depleted conditions, is able to mimic sterol-mediated down-regulation. Either further truncation of the promoter region or mutation of the putative SREBP-binding sequence (5'-GCAGCCCAC-3', -124 to -116 base pairs) abolishes the sterol- and SREBP-dependent transcriptional regulation. Gel mobility shift assay showed that recombinant SREBP-2-(1-481) is able to bind the sequence. Enforced expression of a truncated form of SREBP-2 (amino acids 31-481), which acts as an inhibitor of transcription of the low density lipoprotein receptor gene because it lacks the transcriptional activation domain, also diminishes the luciferase activity, suggesting that direct binding to the promoter region might be sufficient and that the mechanism by which SREBPs inhibit MTP gene expression is distinct from that for the transcriptional stimulation of sterol-regulated genes. Although the SREBP-binding site overlaps a negative insulin-responsive element, insulin negatively regulates MTP gene expression even when the amount of the active form of SREBPs is quite low under the sterol-loaded conditions, indicating that SREBPs only slightly mediate, if at all, the insulin effects. Overall, we conclude that SREBPs are responsible for regulation of lipoprotein secretion via their control of MTP gene expression. Moreover, our results describe for the first time a novel mechanism by which SREBPs negatively regulate expression of the gene encoding the protein involved in lipid metabolism.  (+info)

Transport of lipids from high and low density lipoproteins via scavenger receptor-BI. (7/334)

The scavenger receptor-BI (SR-BI) delivers sterols from circulating lipoproteins to tissues, but the relative potency of individual lipoproteins and the transported cholesterol has not been studied in detail. In this study, we used Chinese hamster ovary cells that express recombinant mouse SR-BI but have no functional low density lipoprotein (LDL) receptors (ldlA7-SRBI cells) to compare the fate of lipids transferred from high or low density lipoproteins to cells by SR-BI. HDL and LDL were equally effective in mediating the transfer of [(3)H]cholesterol to cells. Only 5% of the free cholesterol transferred to cells was esterified, in direct contrast to the findings in the cells that express LDL receptors in which 50% of the transported cholesterol was esterified. Almost all the free cholesterol transferred from lipoproteins to cells was rapidly excreted when the ldlA7-SRBI cells were switched to media containing unlabeled lipoproteins. SR-BI expression was associated with an increase in selective cholesteryl ester uptake from both lipoproteins, but HDL was a more effective donor. HDL and LDL were equally effective in delivering cholesterol to the intracellular regulatory pool via SR-BI. These data indicate that SR-BI is able to exchange cholesterol rapidly between lipoproteins and cell membranes and can mediate the uptake of cholesteryl esters from both classes of lipoproteins.  (+info)

Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. (8/334)

Sterol regulatory element binding proteins (SREBPs) enhance transcription of genes encoding enzymes of cholesterol and fatty acid biosynthesis and uptake. In the current experiments, we observed a decline in the mRNA encoding one SREBP isoform, SREBP-1c, in the livers of rats that were rendered diabetic by treatment with streptozotocin. There was no change in the mRNA encoding SREBP-1a, which is derived from the same gene as SREBP-1c but uses a different promoter. The ratio of SREBP-1c:1a transcripts fell 25-fold from 5:1 in control rats to 0.2:1 in the diabetic animals. The SREBP-1c mRNA rose nearly to normal, and the 1c:1a ratio increased 17-fold when the diabetic rats were treated for 6 h with insulin. These treatments produced no change in the mRNA for SREBP-2, which is encoded by a separate gene. The SREBP-1c mRNA also fell selectively in freshly isolated rat hepatocytes and rose when the cells were treated with insulin. Considered together with recent data on hepatocytes [Foretz, M., Pacot, C., Dugal, I., et al. (1999) Mol. Cell. Biol. 19, 3760-3768], the current in vivo studies suggest that insulin may stimulate lipid synthesis in the liver by selectively inducing transcription of the SREBP-1c gene.  (+info)

Sterol Regulatory Element Binding Protein 1 (SREBP-1) is a transcription factor that plays a crucial role in the regulation of lipid metabolism, primarily cholesterol and fatty acid biosynthesis. It binds to specific DNA sequences called sterol regulatory elements (SREs), which are present in the promoter regions of genes involved in lipid synthesis.

SREBP-1 exists in two isoforms, SREBP-1a and SREBP-1c, encoded by a single gene through alternative splicing. SREBP-1a is a stronger transcriptional activator than SREBP-1c and can activate both cholesterol and fatty acid synthesis genes. In contrast, SREBP-1c primarily regulates fatty acid synthesis genes.

Under normal conditions, SREBP-1 is found in the endoplasmic reticulum (ER) membrane as an inactive precursor bound to another protein called SREBP cleavage-activating protein (SCAP). When cells detect low levels of cholesterol or fatty acids, SCAP escorts SREBP-1 to the Golgi apparatus, where it undergoes proteolytic processing to release the active transcription factor. The active SREBP-1 then translocates to the nucleus and binds to SREs, promoting the expression of genes involved in lipid synthesis.

Overall, SREBP-1 is a critical regulator of lipid homeostasis, and its dysregulation has been implicated in various diseases, including obesity, insulin resistance, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis.

Sterol Regulatory Element Binding Protein 2 (SREBP-2) is a transcription factor that plays a crucial role in the regulation of cholesterol homeostasis in the body. It is a member of the SREBP family, which also includes SREBP-1a and SREBP-1c, and is encoded by the SREBF2 gene.

SREBP-2 is primarily involved in the regulation of genes that are necessary for cholesterol synthesis and uptake. When cholesterol levels in the body are low, SREBP-2 gets activated and moves from the endoplasmic reticulum to the Golgi apparatus, where it undergoes proteolytic cleavage to release its active form. The active SREBP-2 then translocates to the nucleus and binds to sterol regulatory elements (SREs) in the promoter regions of target genes, thereby inducing their transcription.

The target genes of SREBP-2 include HMG-CoA reductase, which is a rate-limiting enzyme in cholesterol synthesis, and LDL receptor, which is responsible for the uptake of low-density lipoprotein (LDL) or "bad" cholesterol from the bloodstream. By upregulating the expression of these genes, SREBP-2 helps to increase cholesterol levels in the body and maintain cholesterol homeostasis.

Dysregulation of SREBP-2 has been implicated in various diseases, including atherosclerosis, cardiovascular disease, and cancer.

Sterol Regulatory Element Binding Proteins (SREBPs) are a family of transcription factors that play crucial roles in regulating the synthesis and uptake of cholesterol, fatty acids, triglycerides, and other lipids in the body. They do so by controlling the expression of genes involved in these metabolic pathways.

SREBPs are activated in response to low cellular levels of cholesterol or fatty acids. When activated, they bind to specific DNA sequences called sterol regulatory elements (SREs) in the promoter regions of their target genes, promoting their transcription and leading to increased synthesis and uptake of lipids.

There are three main isoforms of SREBPs: SREBP-1a, SREBP-1c, and SREBP-2. SREBP-1a and SREBP-1c primarily regulate the expression of genes involved in fatty acid synthesis, while SREBP-2 mainly regulates cholesterol synthesis and uptake. Dysregulation of SREBP activity has been implicated in various metabolic disorders, including obesity, insulin resistance, and atherosclerosis.

CCAAT-Enhancer-Binding Proteins (C/EBPs) are a family of transcription factors that play crucial roles in the regulation of various biological processes, including cell growth, development, and differentiation. They bind to specific DNA sequences called CCAAT boxes, which are found in the promoter or enhancer regions of many genes.

The C/EBP family consists of several members, including C/EBPα, C/EBPβ, C/EBPγ, C/EBPδ, and C/EBPε. These proteins share a highly conserved basic region-leucine zipper (bZIP) domain, which is responsible for their DNA-binding and dimerization activities.

C/EBPs can form homodimers or heterodimers with other bZIP proteins, allowing them to regulate gene expression in a combinatorial manner. They are involved in the regulation of various physiological processes, such as inflammation, immune response, metabolism, and cell cycle control. Dysregulation of C/EBP function has been implicated in several diseases, including cancer, diabetes, and inflammatory disorders.

Sterols are a type of organic compound that is derived from steroids and found in the cell membranes of organisms. In animals, including humans, cholesterol is the most well-known sterol. Sterols help to maintain the structural integrity and fluidity of cell membranes, and they also play important roles as precursors for the synthesis of various hormones and other signaling molecules. Phytosterols are plant sterols that have been shown to have cholesterol-lowering effects in humans when consumed in sufficient amounts.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Lipogenesis is the biological process by which fatty acids are synthesized and stored as lipids or fat in living organisms. This process occurs primarily in the liver and adipose tissue, with excess glucose being converted into fatty acids and then esterified to form triglycerides. These triglycerides are then packaged with proteins and cholesterol to form lipoproteins, which are transported throughout the body for energy storage or use. Lipogenesis is a complex process involving multiple enzymes and metabolic pathways, and it is tightly regulated by hormones such as insulin, glucagon, and adrenaline. Disorders of lipogenesis can lead to conditions such as obesity, fatty liver disease, and metabolic disorders.

Fatty acid synthases (FAS) are a group of enzymes that are responsible for the synthesis of fatty acids in the body. They catalyze a series of reactions that convert acetyl-CoA and malonyl-CoA into longer chain fatty acids, which are then used for various purposes such as energy storage or membrane formation.

The human genome encodes two types of FAS: type I and type II. Type I FAS is a large multifunctional enzyme complex found in the cytoplasm of cells, while type II FAS consists of individual enzymes located in the mitochondria. Both types of FAS play important roles in lipid metabolism, but their regulation and expression differ depending on the tissue and physiological conditions.

Inhibition of FAS has been explored as a potential therapeutic strategy for various diseases, including cancer, obesity, and metabolic disorders. However, more research is needed to fully understand the complex mechanisms regulating FAS activity and its role in human health and disease.

Hydroxymethylglutaryl-CoA Synthase (HMG-CoA Synthase) is a key enzyme in the cholesterol biosynthesis pathway. It catalyzes the reaction of acetoacetyl-CoA and acetyl-CoA to form HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A), which is a crucial intermediate in the synthesis of cholesterol, ketone bodies, and other isoprenoids.

There are two isoforms of this enzyme: HMG-CoA synthase 1 (HMGCS1) and HMG-CoA synthase 2 (HMGCS2). HMGCS1 is primarily expressed in the liver and is involved in cholesterol synthesis, while HMGCS2 is mainly found in the brain, kidney, and liver, where it plays a role in ketone body synthesis during periods of fasting or low-carbohydrate diets.

Defects in HMG-CoA synthase can lead to metabolic disorders, such as hypocholesterolemia (low cholesterol levels) and hyperketonemia (elevated ketone bodies). Additionally, inhibitors of HMG-CoA synthase are used as cholesterol-lowering drugs, known as statins, to treat conditions like hyperlipidemia and prevent cardiovascular diseases.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

"Nostoc commune" is not a medical term, but a scientific name for a type of cyanobacteria (blue-green algae). It's commonly found in various environments such as freshwater, soil, and on rocks. This organism can form colonies that appear as slimy, dark green or black mats.

While not a direct medical term, certain species of cyanobacteria, including Nostoc commune, can produce toxins that may pose health risks to humans and animals if ingested, inhaled, or contact skin. These toxins can cause various symptoms, such as rashes, nausea, vomiting, diarrhea, and liver damage. However, not all strains of Nostoc commune produce toxins, and the health risks associated with this specific species are relatively low compared to other cyanobacteria.

Nonetheless, it is essential to be aware of potential health hazards when encountering cyanobacterial blooms in recreational water bodies or drinking water sources and follow local guidelines for reporting and managing such incidents.

Cholesterol is a type of lipid (fat) molecule that is an essential component of cell membranes and is also used to make certain hormones and vitamins in the body. It is produced by the liver and is also obtained from animal-derived foods such as meat, dairy products, and eggs.

Cholesterol does not mix with blood, so it is transported through the bloodstream by lipoproteins, which are particles made up of both lipids and proteins. There are two main types of lipoproteins that carry cholesterol: low-density lipoproteins (LDL), also known as "bad" cholesterol, and high-density lipoproteins (HDL), also known as "good" cholesterol.

High levels of LDL cholesterol in the blood can lead to a buildup of cholesterol in the walls of the arteries, increasing the risk of heart disease and stroke. On the other hand, high levels of HDL cholesterol are associated with a lower risk of these conditions because HDL helps remove LDL cholesterol from the bloodstream and transport it back to the liver for disposal.

It is important to maintain healthy levels of cholesterol through a balanced diet, regular exercise, and sometimes medication if necessary. Regular screening is also recommended to monitor cholesterol levels and prevent health complications.

Lipid metabolism is the process by which the body breaks down and utilizes lipids (fats) for various functions, such as energy production, cell membrane formation, and hormone synthesis. This complex process involves several enzymes and pathways that regulate the digestion, absorption, transport, storage, and consumption of fats in the body.

The main types of lipids involved in metabolism include triglycerides, cholesterol, phospholipids, and fatty acids. The breakdown of these lipids begins in the digestive system, where enzymes called lipases break down dietary fats into smaller molecules called fatty acids and glycerol. These molecules are then absorbed into the bloodstream and transported to the liver, which is the main site of lipid metabolism.

In the liver, fatty acids may be further broken down for energy production or used to synthesize new lipids. Excess fatty acids may be stored as triglycerides in specialized cells called adipocytes (fat cells) for later use. Cholesterol is also metabolized in the liver, where it may be used to synthesize bile acids, steroid hormones, and other important molecules.

Disorders of lipid metabolism can lead to a range of health problems, including obesity, diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). These conditions may be caused by genetic factors, lifestyle habits, or a combination of both. Proper diagnosis and management of lipid metabolism disorders typically involves a combination of dietary changes, exercise, and medication.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

Geranyltranstransferase is not a commonly used medical term, but it is a type of enzyme involved in the biosynthesis of various compounds in the body. According to biochemistry and molecular biology resources, Geranyltranstransferase (GTT) is an enzyme that catalyzes the head-to-tail condensation of geranyl diphosphate with isopentenyl diphosphate to form farnesyl diphosphate.

Farnesyl diphosphate is a key intermediate in the biosynthesis of steroids, sesquiterpenes, and other isoprenoid compounds. These compounds have diverse functions in the body, including serving as components of cell membranes, hormones, and signaling molecules.

In summary, Geranyltranstransferase is a biochemical term that refers to an enzyme involved in the biosynthesis of various isoprenoid compounds through the condensation of geranyl diphosphate with isopentenyl diphosphate.

Stearoyl-CoA desaturase (SCD) is an enzyme that plays a crucial role in the synthesis of monounsaturated fatty acids (MUFAs) in the body. Specifically, SCD catalyzes the conversion of saturated fatty acids, such as stearic acid and palmitic acid, into MUFAs by introducing a double bond into their carbon chain.

The two main isoforms of SCD in humans are SCD1 and SCD5, with SCD1 being the most well-studied. SCD1 is primarily located in the endoplasmic reticulum of cells in various tissues, including the liver, adipose tissue, and skin.

The regulation of SCD activity has important implications for human health, as MUFAs are essential components of cell membranes and play a role in maintaining their fluidity and functionality. Additionally, abnormal levels of SCD activity have been linked to several diseases, including obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. Therefore, understanding the function and regulation of SCD is an active area of research in the field of lipid metabolism and related diseases.

I'm sorry for any confusion, but the term "Leucine Zippers" is not a medical term or concept. It is a term used in molecular biology to describe a specific structural motif found in some proteins. Leucine zippers are amino acid sequences that contain regularly spaced leucine residues and form coiled-coil structures, which play a role in protein-protein interactions, particularly in DNA binding transcription factors.

If you have any questions related to medical terminology or concepts, I would be happy to help!

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

LDL receptors (Low-Density Lipoprotein Receptors) are cell surface receptors that play a crucial role in the regulation of cholesterol homeostasis within the body. They are responsible for recognizing and binding to LDL particles, also known as "bad cholesterol," which are then internalized by the cell through endocytosis.

Once inside the cell, the LDL particles are broken down, releasing their cholesterol content, which can be used for various cellular processes such as membrane synthesis and hormone production. The LDL receptors themselves are recycled back to the cell surface, allowing for continued uptake of LDL particles.

Mutations in the LDL receptor gene can lead to a condition called familial hypercholesterolemia, which is characterized by high levels of LDL cholesterol in the blood and an increased risk of premature cardiovascular disease.

The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:

1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.

Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.

Hydroxymethylglutaryl CoA (HMG-CoA) reductase is an enzyme that plays a crucial role in the synthesis of cholesterol in the body. It is found in the endoplasmic reticulum of cells and catalyzes the conversion of HMG-CoA to mevalonic acid, which is a key rate-limiting step in the cholesterol biosynthetic pathway.

The reaction catalyzed by HMG-CoA reductase is as follows:

HMG-CoA + 2 NADPH + 2 H+ → mevalonic acid + CoA + 2 NADP+

This enzyme is the target of statin drugs, which are commonly prescribed to lower cholesterol levels in the treatment of cardiovascular diseases. Statins work by inhibiting HMG-CoA reductase, thereby reducing the production of cholesterol in the body.

Hydroxycholesterols are a type of sterol that is formed in the body when cholesterol, a steroid alcohol, undergoes hydroxylation. This means that one or more hydroxyl groups (-OH) are added to the cholesterol molecule. There are several different types of hydroxycholesterols, including 24-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol, among others. These compounds play important roles in various physiological processes, such as regulating cholesterol metabolism and contributing to the formation of bile acids. They have also been studied for their potential involvement in atherosclerosis, Alzheimer's disease, and other health conditions.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Acetyl-CoA carboxylase (ACCA) is a biotin-dependent enzyme that plays a crucial role in fatty acid synthesis. It catalyzes the conversion of acetyl-CoA to malonyl-CoA, which is the first and rate-limiting step in the synthesis of long-chain fatty acids. The reaction catalyzed by ACCA is as follows:

acetyl-CoA + HCO3- + ATP + 2H+ --> malonyl-CoA + CoA + ADP + Pi + 2H2O

ACCA exists in two isoforms, a cytosolic form (ACC1) and a mitochondrial form (ACC2). ACC1 is primarily involved in fatty acid synthesis, while ACC2 is responsible for the regulation of fatty acid oxidation. The activity of ACCA is regulated by several factors, including phosphorylation/dephosphorylation, allosteric regulation, and transcriptional regulation. Dysregulation of ACCA has been implicated in various metabolic disorders, such as obesity, insulin resistance, and non-alcoholic fatty liver disease.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

CREB (Cyclic AMP Response Element-Binding Protein) is a transcription factor that plays a crucial role in regulating gene expression in response to various cellular signals. CREB binds to the cAMP response element (CRE) sequence in the promoter region of target genes and regulates their transcription.

When activated, CREB undergoes phosphorylation at a specific serine residue (Ser-133), which leads to its binding to the coactivator protein CBP/p300 and recruitment of additional transcriptional machinery to the promoter region. This results in the activation of target gene transcription.

CREB is involved in various cellular processes, including metabolism, differentiation, survival, and memory formation. Dysregulation of CREB has been implicated in several diseases, such as cancer, neurodegenerative disorders, and mood disorders.

Helix-loop-helix (HLH) motifs are structural domains found in certain proteins, particularly transcription factors, that play a crucial role in DNA binding and protein-protein interactions. These motifs consist of two amphipathic α-helices connected by a loop region. The first helix is known as the "helix-1" or "recognition helix," while the second one is called the "helix-2" or "dimerization helix."

In many HLH proteins, the helices come together to form a dimer through interactions between their hydrophobic residues located in the core of the helix-2. This dimerization enables DNA binding by positioning the recognition helices in close proximity to each other and allowing them to interact with specific DNA sequences, often referred to as E-box motifs (CANNTG).

HLH motifs can be further classified into basic HLH (bHLH) proteins and HLH-only proteins. bHLH proteins contain a basic region adjacent to the N-terminal end of the first helix, which facilitates DNA binding. In contrast, HLH-only proteins lack this basic region and primarily function as dimerization partners for bHLH proteins or participate in other protein-protein interactions.

These motifs are involved in various cellular processes, including cell fate determination, differentiation, proliferation, and apoptosis. Dysregulation of HLH proteins has been implicated in several diseases, such as cancer and neurodevelopmental disorders.

Orphan nuclear receptors are a subfamily of nuclear receptor proteins that are classified as "orphans" because their specific endogenous ligands (natural activating molecules) have not yet been identified. These receptors are still functional transcription factors, which means they can bind to specific DNA sequences and regulate the expression of target genes when activated by a ligand. However, in the case of orphan nuclear receptors, the identity of these ligands remains unknown or unconfirmed.

These receptors play crucial roles in various biological processes, including development, metabolism, and homeostasis. Some orphan nuclear receptors have been found to bind to synthetic ligands (man-made molecules), which has led to the development of potential therapeutic agents for various diseases. Over time, as research progresses, some orphan nuclear receptors may eventually have their endogenous ligands identified and be reclassified as non-orphan nuclear receptors.

Fatty acids are carboxylic acids with a long aliphatic chain, which are important components of lipids and are widely distributed in living organisms. They can be classified based on the length of their carbon chain, saturation level (presence or absence of double bonds), and other structural features.

The two main types of fatty acids are:

1. Saturated fatty acids: These have no double bonds in their carbon chain and are typically solid at room temperature. Examples include palmitic acid (C16:0) and stearic acid (C18:0).
2. Unsaturated fatty acids: These contain one or more double bonds in their carbon chain and can be further classified into monounsaturated (one double bond) and polyunsaturated (two or more double bonds) fatty acids. Examples of unsaturated fatty acids include oleic acid (C18:1, monounsaturated), linoleic acid (C18:2, polyunsaturated), and alpha-linolenic acid (C18:3, polyunsaturated).

Fatty acids play crucial roles in various biological processes, such as energy storage, membrane structure, and cell signaling. Some essential fatty acids cannot be synthesized by the human body and must be obtained through dietary sources.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Gene expression regulation, enzymologic refers to the biochemical processes and mechanisms that control the transcription and translation of specific genes into functional proteins or enzymes. This regulation is achieved through various enzymatic activities that can either activate or repress gene expression at different levels, such as chromatin remodeling, transcription factor activation, mRNA processing, and protein degradation.

Enzymologic regulation of gene expression involves the action of specific enzymes that catalyze chemical reactions involved in these processes. For example, histone-modifying enzymes can alter the structure of chromatin to make genes more or less accessible for transcription, while RNA polymerase and its associated factors are responsible for transcribing DNA into mRNA. Additionally, various enzymes are involved in post-transcriptional modifications of mRNA, such as splicing, capping, and tailing, which can affect the stability and translation of the transcript.

Overall, the enzymologic regulation of gene expression is a complex and dynamic process that allows cells to respond to changes in their environment and maintain proper physiological function.

Lipids are a broad group of organic compounds that are insoluble in water but soluble in nonpolar organic solvents. They include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides, and phospholipids. Lipids serve many important functions in the body, including energy storage, acting as structural components of cell membranes, and serving as signaling molecules. High levels of certain lipids, particularly cholesterol and triglycerides, in the blood are associated with an increased risk of cardiovascular disease.

Fatty liver, also known as hepatic steatosis, is a medical condition characterized by the abnormal accumulation of fat in the liver. The liver's primary function is to process nutrients, filter blood, and fight infections, among other tasks. When excess fat builds up in the liver cells, it can impair liver function and lead to inflammation, scarring, and even liver failure if left untreated.

Fatty liver can be caused by various factors, including alcohol consumption, obesity, nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and certain medications or medical conditions. NAFLD is the most common cause of fatty liver in the United States and other developed countries, affecting up to 25% of the population.

Symptoms of fatty liver may include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain or discomfort, and jaundice (yellowing of the skin and eyes). However, many people with fatty liver do not experience any symptoms, making it essential to diagnose and manage the condition through regular check-ups and blood tests.

Treatment for fatty liver depends on the underlying cause. Lifestyle changes such as weight loss, exercise, and dietary modifications are often recommended for people with NAFLD or alcohol-related fatty liver disease. Medications may also be prescribed to manage related conditions such as diabetes, high cholesterol, or metabolic syndrome. In severe cases of liver damage, a liver transplant may be necessary.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Membrane proteins are a type of protein that are embedded in the lipid bilayer of biological membranes, such as the plasma membrane of cells or the inner membrane of mitochondria. These proteins play crucial roles in various cellular processes, including:

1. Cell-cell recognition and signaling
2. Transport of molecules across the membrane (selective permeability)
3. Enzymatic reactions at the membrane surface
4. Energy transduction and conversion
5. Mechanosensation and signal transduction

Membrane proteins can be classified into two main categories: integral membrane proteins, which are permanently associated with the lipid bilayer, and peripheral membrane proteins, which are temporarily or loosely attached to the membrane surface. Integral membrane proteins can further be divided into three subcategories based on their topology:

1. Transmembrane proteins, which span the entire width of the lipid bilayer with one or more alpha-helices or beta-barrels.
2. Lipid-anchored proteins, which are covalently attached to lipids in the membrane via a glycosylphosphatidylinositol (GPI) anchor or other lipid modifications.
3. Monotopic proteins, which are partially embedded in the membrane and have one or more domains exposed to either side of the bilayer.

Membrane proteins are essential for maintaining cellular homeostasis and are targets for various therapeutic interventions, including drug development and gene therapy. However, their structural complexity and hydrophobicity make them challenging to study using traditional biochemical methods, requiring specialized techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and single-particle cryo-electron microscopy (cryo-EM).

Fatty acid synthase (FAS) is a multi-enzyme complex that plays a crucial role in the synthesis of long-chain fatty acids in the body. There are two main types of FAS: type I and type II.

Type I fatty acid synthase, also known as FASN, is found primarily in the cytoplasm of cells in tissues such as the liver, adipose tissue, and lactating mammary glands. It is a large protein made up of several distinct enzymatic domains that work together to synthesize long-chain fatty acids from acetyl-CoA and malonyl-CoA.

The process of fatty acid synthesis involves a series of reactions, starting with the condensation of acetyl-CoA and malonyl-CoA to form acetoacetyl-CoA. This reaction is followed by a series of reductions, dehydrations, and another reduction to form a saturated fatty acid molecule with 16 carbons (palmitate).

Type I FAS is often upregulated in conditions associated with increased lipogenesis, such as obesity, metabolic syndrome, and certain types of cancer. Inhibiting FAS has been explored as a potential therapeutic strategy for treating these conditions.

Intracellular signaling peptides and proteins are molecules that play a crucial role in transmitting signals within cells, which ultimately lead to changes in cell behavior or function. These signals can originate from outside the cell (extracellular) or within the cell itself. Intracellular signaling molecules include various types of peptides and proteins, such as:

1. G-protein coupled receptors (GPCRs): These are seven-transmembrane domain receptors that bind to extracellular signaling molecules like hormones, neurotransmitters, or chemokines. Upon activation, they initiate a cascade of intracellular signals through G proteins and secondary messengers.
2. Receptor tyrosine kinases (RTKs): These are transmembrane receptors that bind to growth factors, cytokines, or hormones. Activation of RTKs leads to autophosphorylation of specific tyrosine residues, creating binding sites for intracellular signaling proteins such as adapter proteins, phosphatases, and enzymes like Ras, PI3K, and Src family kinases.
3. Second messenger systems: Intracellular second messengers are small molecules that amplify and propagate signals within the cell. Examples include cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), diacylglycerol (DAG), inositol triphosphate (IP3), calcium ions (Ca2+), and nitric oxide (NO). These second messengers activate or inhibit various downstream effectors, leading to changes in cellular responses.
4. Signal transduction cascades: Intracellular signaling proteins often form complex networks of interacting molecules that relay signals from the plasma membrane to the nucleus. These cascades involve kinases (protein kinases A, B, C, etc.), phosphatases, and adapter proteins, which ultimately regulate gene expression, cell cycle progression, metabolism, and other cellular processes.
5. Ubiquitination and proteasome degradation: Intracellular signaling pathways can also control protein stability by modulating ubiquitin-proteasome degradation. E3 ubiquitin ligases recognize specific substrates and conjugate them with ubiquitin molecules, targeting them for proteasomal degradation. This process regulates the abundance of key signaling proteins and contributes to signal termination or amplification.

In summary, intracellular signaling pathways involve a complex network of interacting proteins that relay signals from the plasma membrane to various cellular compartments, ultimately regulating gene expression, metabolism, and other cellular processes. Dysregulation of these pathways can contribute to disease development and progression, making them attractive targets for therapeutic intervention.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

Adipocytes are specialized cells that comprise adipose tissue, also known as fat tissue. They are responsible for storing energy in the form of lipids, particularly triglycerides, and releasing energy when needed through a process called lipolysis. There are two main types of adipocytes: white adipocytes and brown adipocytes. White adipocytes primarily store energy, while brown adipocytes dissipate energy as heat through the action of uncoupling protein 1 (UCP1).

In addition to their role in energy metabolism, adipocytes also secrete various hormones and signaling molecules that contribute to whole-body homeostasis. These include leptin, adiponectin, resistin, and inflammatory cytokines. Dysregulation of adipocyte function has been implicated in the development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Farnesyl-diphosphate farnesyltransferase is an enzyme that plays a role in the post-translational modification of proteins, specifically by adding a farnesyl group to certain protein substrates. This process is known as farnesylation and it is essential for the localization and function of many proteins, including Ras family GTPases, which are involved in signal transduction pathways that regulate cell growth and differentiation.

The enzyme catalyzes the transfer of a farnesyl group from farnesyl diphosphate (FPP) to a cysteine residue located near the C-terminus of the protein substrate. This reaction occurs in the endoplasmic reticulum and is an essential step in the biosynthesis of many isoprenoid-modified proteins.

Inhibitors of farnesyl-diphosphate farnesyltransferase have been developed as potential therapeutic agents for the treatment of various diseases, including cancer, where aberrant Ras signaling has been implicated in tumor development and progression.

Insulin is a hormone produced by the beta cells of the pancreatic islets, primarily in response to elevated levels of glucose in the circulating blood. It plays a crucial role in regulating blood glucose levels and facilitating the uptake and utilization of glucose by peripheral tissues, such as muscle and adipose tissue, for energy production and storage. Insulin also inhibits glucose production in the liver and promotes the storage of excess glucose as glycogen or triglycerides.

Deficiency in insulin secretion or action leads to impaired glucose regulation and can result in conditions such as diabetes mellitus, characterized by chronic hyperglycemia and associated complications. Exogenous insulin is used as a replacement therapy in individuals with diabetes to help manage their blood glucose levels and prevent long-term complications.

Triglycerides are the most common type of fat in the body, and they're found in the food we eat. They're carried in the bloodstream to provide energy to the cells in our body. High levels of triglycerides in the blood can increase the risk of heart disease, especially in combination with other risk factors such as high LDL (bad) cholesterol, low HDL (good) cholesterol, and high blood pressure.

It's important to note that while triglycerides are a type of fat, they should not be confused with cholesterol, which is a waxy substance found in the cells of our body. Both triglycerides and cholesterol are important for maintaining good health, but high levels of either can increase the risk of heart disease.

Triglyceride levels are measured through a blood test called a lipid panel or lipid profile. A normal triglyceride level is less than 150 mg/dL. Borderline-high levels range from 150 to 199 mg/dL, high levels range from 200 to 499 mg/dL, and very high levels are 500 mg/dL or higher.

Elevated triglycerides can be caused by various factors such as obesity, physical inactivity, excessive alcohol consumption, smoking, and certain medical conditions like diabetes, hypothyroidism, and kidney disease. Medications such as beta-blockers, steroids, and diuretics can also raise triglyceride levels.

Lifestyle changes such as losing weight, exercising regularly, eating a healthy diet low in saturated and trans fats, avoiding excessive alcohol consumption, and quitting smoking can help lower triglyceride levels. In some cases, medication may be necessary to reduce triglycerides to recommended levels.

Post-translational protein processing refers to the modifications and changes that proteins undergo after their synthesis on ribosomes, which are complex molecular machines responsible for protein synthesis. These modifications occur through various biochemical processes and play a crucial role in determining the final structure, function, and stability of the protein.

The process begins with the translation of messenger RNA (mRNA) into a linear polypeptide chain, which is then subjected to several post-translational modifications. These modifications can include:

1. Proteolytic cleavage: The removal of specific segments or domains from the polypeptide chain by proteases, resulting in the formation of mature, functional protein subunits.
2. Chemical modifications: Addition or modification of chemical groups to the side chains of amino acids, such as phosphorylation (addition of a phosphate group), glycosylation (addition of sugar moieties), methylation (addition of a methyl group), acetylation (addition of an acetyl group), and ubiquitination (addition of a ubiquitin protein).
3. Disulfide bond formation: The oxidation of specific cysteine residues within the polypeptide chain, leading to the formation of disulfide bonds between them. This process helps stabilize the three-dimensional structure of proteins, particularly in extracellular environments.
4. Folding and assembly: The acquisition of a specific three-dimensional conformation by the polypeptide chain, which is essential for its function. Chaperone proteins assist in this process to ensure proper folding and prevent aggregation.
5. Protein targeting: The directed transport of proteins to their appropriate cellular locations, such as the nucleus, mitochondria, endoplasmic reticulum, or plasma membrane. This is often facilitated by specific signal sequences within the protein that are recognized and bound by transport machinery.

Collectively, these post-translational modifications contribute to the functional diversity of proteins in living organisms, allowing them to perform a wide range of cellular processes, including signaling, catalysis, regulation, and structural support.

"Response elements" is a term used in molecular biology, particularly in the study of gene regulation. Response elements are specific DNA sequences that can bind to transcription factors, which are proteins that regulate gene expression. When a transcription factor binds to a response element, it can either activate or repress the transcription of the nearby gene.

Response elements are often found in the promoter region of genes and are typically short, conserved sequences that can be recognized by specific transcription factors. The binding of a transcription factor to a response element can lead to changes in chromatin structure, recruitment of co-activators or co-repressors, and ultimately, the regulation of gene expression.

Response elements are important for many biological processes, including development, differentiation, and response to environmental stimuli such as hormones, growth factors, and stress. The specificity of transcription factor binding to response elements allows for precise control of gene expression in response to changing conditions within the cell or organism.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Regulatory sequences in nucleic acid refer to specific DNA or RNA segments that control the spatial and temporal expression of genes without encoding proteins. They are crucial for the proper functioning of cells as they regulate various cellular processes such as transcription, translation, mRNA stability, and localization. Regulatory sequences can be found in both coding and non-coding regions of DNA or RNA.

Some common types of regulatory sequences in nucleic acid include:

1. Promoters: DNA sequences typically located upstream of the gene that provide a binding site for RNA polymerase and transcription factors to initiate transcription.
2. Enhancers: DNA sequences, often located at a distance from the gene, that enhance transcription by binding to specific transcription factors and increasing the recruitment of RNA polymerase.
3. Silencers: DNA sequences that repress transcription by binding to specific proteins that inhibit the recruitment of RNA polymerase or promote chromatin compaction.
4. Intron splice sites: Specific nucleotide sequences within introns (non-coding regions) that mark the boundaries between exons (coding regions) and are essential for correct splicing of pre-mRNA.
5. 5' untranslated regions (UTRs): Regions located at the 5' end of an mRNA molecule that contain regulatory elements affecting translation efficiency, stability, and localization.
6. 3' untranslated regions (UTRs): Regions located at the 3' end of an mRNA molecule that contain regulatory elements influencing translation termination, stability, and localization.
7. miRNA target sites: Specific sequences in mRNAs that bind to microRNAs (miRNAs) leading to translational repression or degradation of the target mRNA.

Fluorinated hydrocarbons are organic compounds that contain fluorine and carbon atoms. These compounds can be classified into two main groups: fluorocarbons (which consist only of fluorine and carbon) and fluorinated aliphatic or aromatic hydrocarbons (which contain hydrogen in addition to fluorine and carbon).

Fluorocarbons are further divided into three categories: fully fluorinated compounds (perfluorocarbons, PFCs), partially fluorinated compounds (hydrochlorofluorocarbons, HCFCs, and hydrofluorocarbons, HFCs), and chlorofluorocarbons (CFCs). These compounds have been widely used as refrigerants, aerosol propellants, fire extinguishing agents, and cleaning solvents due to their chemical stability, low toxicity, and non-flammability.

Fluorinated aliphatic or aromatic hydrocarbons are organic compounds that contain fluorine, carbon, and hydrogen atoms. Examples include fluorinated alcohols, ethers, amines, and halogenated compounds. These compounds have a wide range of applications in industry, medicine, and research due to their unique chemical properties.

It is important to note that some fluorinated hydrocarbons can contribute to the depletion of the ozone layer and global warming, making it essential to regulate their use and production.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

CREB-binding protein (CBP) is a transcription coactivator that plays a crucial role in regulating gene expression. It is called a "coactivator" because it works together with other proteins, such as transcription factors, to enhance the process of gene transcription. CBP is so named because it can bind to the cAMP response element-binding (CREB) protein, which is a transcription factor that regulates the expression of various genes in response to different signals within cells.

CBP has intrinsic histone acetyltransferase (HAT) activity, which means it can add acetyl groups to histone proteins around which DNA is wound. This modification loosens the chromatin structure, making it more accessible for transcription factors and other proteins involved in gene expression. As a result, CBP acts as a global regulator of gene expression, influencing various cellular processes such as development, differentiation, and homeostasis.

Mutations in the CBP gene have been associated with several human diseases, including Rubinstein-Taybi syndrome, a rare genetic disorder characterized by growth retardation, mental deficiency, and distinct facial features. Additionally, CBP has been implicated in cancer, as its dysregulation can lead to uncontrolled cell growth and malignant transformation.

Luciferases are a class of enzymes that catalyze the oxidation of their substrates, leading to the emission of light. This bioluminescent process is often associated with certain species of bacteria, insects, and fish. The term "luciferase" comes from the Latin word "lucifer," which means "light bearer."

The most well-known example of luciferase is probably that found in fireflies, where the enzyme reacts with a compound called luciferin to produce light. This reaction requires the presence of oxygen and ATP (adenosine triphosphate), which provides the energy needed for the reaction to occur.

Luciferases have important applications in scientific research, particularly in the development of sensitive assays for detecting gene expression and protein-protein interactions. By labeling a protein or gene of interest with luciferase, researchers can measure its activity by detecting the light emitted during the enzymatic reaction. This allows for highly sensitive and specific measurements, making luciferases valuable tools in molecular biology and biochemistry.

Transcriptional regulatory elements are specific DNA sequences within the genome that bind to proteins or protein complexes known as transcription factors. These binding interactions control the initiation, rate, and termination of gene transcription, which is the process by which the information encoded in DNA is copied into RNA. Transcriptional regulatory elements can be classified into several categories, including promoters, enhancers, silencers, and insulators.

Promoters are located near the beginning of a gene, usually immediately upstream of the transcription start site. They provide a binding platform for the RNA polymerase enzyme and other general transcription factors that are required to initiate transcription. Promoters often contain a conserved sequence known as the TATA box, which is recognized by the TATA-binding protein (TBP) and helps position the RNA polymerase at the correct location.

Enhancers are DNA sequences that can be located far upstream or downstream of the gene they regulate, sometimes even in introns or exons within the gene itself. They serve to increase the transcription rate of a gene by providing binding sites for specific transcription factors that recruit coactivators and other regulatory proteins. These interactions lead to the formation of an active chromatin structure that facilitates transcription.

Silencers are DNA sequences that, like enhancers, can be located at various distances from the genes they regulate. However, instead of increasing transcription, silencers repress gene expression by binding to transcriptional repressors or corepressors. These proteins recruit chromatin-modifying enzymes that introduce repressive histone modifications or compact the chromatin structure, making it less accessible for transcription factors and RNA polymerase.

Insulators are DNA sequences that act as boundaries between transcriptional regulatory elements, preventing inappropriate interactions between enhancers, silencers, and promoters. Insulators can also protect genes from the effects of nearby chromatin modifications or positioning effects that might otherwise interfere with their normal expression patterns.

Collectively, these transcriptional regulatory elements play a crucial role in ensuring proper gene expression in response to developmental cues, environmental stimuli, and various physiological processes. Dysregulation of these elements can contribute to the development of various diseases, including cancer and genetic disorders.

A "reporter gene" is a type of gene that is linked to a gene of interest in order to make the expression or activity of that gene detectable. The reporter gene encodes for a protein that can be easily measured and serves as an indicator of the presence and activity of the gene of interest. Commonly used reporter genes include those that encode for fluorescent proteins, enzymes that catalyze colorimetric reactions, or proteins that bind to specific molecules.

In the context of genetics and genomics research, a reporter gene is often used in studies involving gene expression, regulation, and function. By introducing the reporter gene into an organism or cell, researchers can monitor the activity of the gene of interest in real-time or after various experimental treatments. The information obtained from these studies can help elucidate the role of specific genes in biological processes and diseases, providing valuable insights for basic research and therapeutic development.

Cytoplasmic receptors and nuclear receptors are two types of intracellular receptors that play crucial roles in signal transduction pathways and regulation of gene expression. They are classified based on their location within the cell. Here are the medical definitions for each:

1. Cytoplasmic Receptors: These are a group of intracellular receptors primarily found in the cytoplasm of cells, which bind to specific hormones, growth factors, or other signaling molecules. Upon binding, these receptors undergo conformational changes that allow them to interact with various partners, such as adapter proteins and enzymes, leading to activation of downstream signaling cascades. These pathways ultimately result in modulation of cellular processes like proliferation, differentiation, and apoptosis. Examples of cytoplasmic receptors include receptor tyrosine kinases (RTKs), serine/threonine kinase receptors, and cytokine receptors.
2. Nuclear Receptors: These are a distinct class of intracellular receptors that reside primarily in the nucleus of cells. They bind to specific ligands, such as steroid hormones, thyroid hormones, vitamin D, retinoic acid, and various other lipophilic molecules. Upon binding, nuclear receptors undergo conformational changes that facilitate their interaction with co-regulatory proteins and the DNA. This interaction results in the modulation of gene transcription, ultimately leading to alterations in protein expression and cellular responses. Examples of nuclear receptors include estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor (TR), vitamin D receptor (VDR), and peroxisome proliferator-activated receptors (PPARs).

Both cytoplasmic and nuclear receptors are essential components of cellular communication networks, allowing cells to respond appropriately to extracellular signals and maintain homeostasis. Dysregulation of these receptors has been implicated in various diseases, including cancer, diabetes, and autoimmune disorders.

Homeostasis is a fundamental concept in the field of medicine and physiology, referring to the body's ability to maintain a stable internal environment, despite changes in external conditions. It is the process by which biological systems regulate their internal environment to remain in a state of dynamic equilibrium. This is achieved through various feedback mechanisms that involve sensors, control centers, and effectors, working together to detect, interpret, and respond to disturbances in the system.

For example, the body maintains homeostasis through mechanisms such as temperature regulation (through sweating or shivering), fluid balance (through kidney function and thirst), and blood glucose levels (through insulin and glucagon secretion). When homeostasis is disrupted, it can lead to disease or dysfunction in the body.

In summary, homeostasis is the maintenance of a stable internal environment within biological systems, through various regulatory mechanisms that respond to changes in external conditions.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Transcriptional activation is the process by which a cell increases the rate of transcription of specific genes from DNA to RNA. This process is tightly regulated and plays a crucial role in various biological processes, including development, differentiation, and response to environmental stimuli.

Transcriptional activation occurs when transcription factors (proteins that bind to specific DNA sequences) interact with the promoter region of a gene and recruit co-activator proteins. These co-activators help to remodel the chromatin structure around the gene, making it more accessible for the transcription machinery to bind and initiate transcription.

Transcriptional activation can be regulated at multiple levels, including the availability and activity of transcription factors, the modification of histone proteins, and the recruitment of co-activators or co-repressors. Dysregulation of transcriptional activation has been implicated in various diseases, including cancer and genetic disorders.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

PPAR-alpha (Peroxisome Proliferator-Activated Receptor alpha) is a type of nuclear receptor protein that functions as a transcription factor, regulating the expression of specific genes involved in lipid metabolism. It plays a crucial role in the breakdown of fatty acids and the synthesis of high-density lipoproteins (HDL or "good" cholesterol) in the liver. PPAR-alpha activation also has anti-inflammatory effects, making it a potential therapeutic target for metabolic disorders such as diabetes, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD).

DNA primers are short single-stranded DNA molecules that serve as a starting point for DNA synthesis. They are typically used in laboratory techniques such as the polymerase chain reaction (PCR) and DNA sequencing. The primer binds to a complementary sequence on the DNA template through base pairing, providing a free 3'-hydroxyl group for the DNA polymerase enzyme to add nucleotides and synthesize a new strand of DNA. This allows for specific and targeted amplification or analysis of a particular region of interest within a larger DNA molecule.

The cell nucleus is a membrane-bound organelle found in the eukaryotic cells (cells with a true nucleus). It contains most of the cell's genetic material, organized as DNA molecules in complex with proteins, RNA molecules, and histones to form chromosomes.

The primary function of the cell nucleus is to regulate and control the activities of the cell, including growth, metabolism, protein synthesis, and reproduction. It also plays a crucial role in the process of mitosis (cell division) by separating and protecting the genetic material during this process. The nuclear membrane, or nuclear envelope, surrounding the nucleus is composed of two lipid bilayers with numerous pores that allow for the selective transport of molecules between the nucleoplasm (nucleus interior) and the cytoplasm (cell exterior).

The cell nucleus is a vital structure in eukaryotic cells, and its dysfunction can lead to various diseases, including cancer and genetic disorders.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.

The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.

Genetic enhancer elements are DNA sequences that increase the transcription of specific genes. They work by binding to regulatory proteins called transcription factors, which in turn recruit RNA polymerase II, the enzyme responsible for transcribing DNA into messenger RNA (mRNA). This results in the activation of gene transcription and increased production of the protein encoded by that gene.

Enhancer elements can be located upstream, downstream, or even within introns of the genes they regulate, and they can act over long distances along the DNA molecule. They are an important mechanism for controlling gene expression in a tissue-specific and developmental stage-specific manner, allowing for the precise regulation of gene activity during embryonic development and throughout adult life.

It's worth noting that genetic enhancer elements are often referred to simply as "enhancers," and they are distinct from other types of regulatory DNA sequences such as promoters, silencers, and insulators.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Adipose tissue, also known as fatty tissue, is a type of connective tissue that is composed mainly of adipocytes (fat cells). It is found throughout the body, but is particularly abundant in the abdominal cavity, beneath the skin, and around organs such as the heart and kidneys.

Adipose tissue serves several important functions in the body. One of its primary roles is to store energy in the form of fat, which can be mobilized and used as an energy source during periods of fasting or exercise. Adipose tissue also provides insulation and cushioning for the body, and produces hormones that help regulate metabolism, appetite, and reproductive function.

There are two main types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is the more common form and is responsible for storing energy as fat. BAT, on the other hand, contains a higher number of mitochondria and is involved in heat production and energy expenditure.

Excessive accumulation of adipose tissue can lead to obesity, which is associated with an increased risk of various health problems such as diabetes, heart disease, and certain types of cancer.

Hepatocytes are the predominant type of cells in the liver, accounting for about 80% of its cytoplasmic mass. They play a key role in protein synthesis, protein storage, transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, detoxification, modification, and excretion of exogenous and endogenous substances, initiation of formation and secretion of bile, and enzyme production. Hepatocytes are essential for the maintenance of homeostasis in the body.

Down-regulation is a process that occurs in response to various stimuli, where the number or sensitivity of cell surface receptors or the expression of specific genes is decreased. This process helps maintain homeostasis within cells and tissues by reducing the ability of cells to respond to certain signals or molecules.

In the context of cell surface receptors, down-regulation can occur through several mechanisms:

1. Receptor internalization: After binding to their ligands, receptors can be internalized into the cell through endocytosis. Once inside the cell, these receptors may be degraded or recycled back to the cell surface in smaller numbers.
2. Reduced receptor synthesis: Down-regulation can also occur at the transcriptional level, where the expression of genes encoding for specific receptors is decreased, leading to fewer receptors being produced.
3. Receptor desensitization: Prolonged exposure to a ligand can lead to a decrease in receptor sensitivity or affinity, making it more difficult for the cell to respond to the signal.

In the context of gene expression, down-regulation refers to the decreased transcription and/or stability of specific mRNAs, leading to reduced protein levels. This process can be induced by various factors, including microRNA (miRNA)-mediated regulation, histone modification, or DNA methylation.

Down-regulation is an essential mechanism in many physiological processes and can also contribute to the development of several diseases, such as cancer and neurodegenerative disorders.

PPAR gamma, or Peroxisome Proliferator-Activated Receptor gamma, is a nuclear receptor protein that functions as a transcription factor. It plays a crucial role in the regulation of genes involved in adipogenesis (the process of forming mature fat cells), lipid metabolism, insulin sensitivity, and glucose homeostasis. PPAR gamma is primarily expressed in adipose tissue but can also be found in other tissues such as the immune system, large intestine, and brain.

PPAR gamma forms a heterodimer with another nuclear receptor protein, RXR (Retinoid X Receptor), and binds to specific DNA sequences called PPREs (Peroxisome Proliferator Response Elements) in the promoter regions of target genes. Upon binding, PPAR gamma modulates the transcription of these genes, either activating or repressing their expression.

Agonists of PPAR gamma, such as thiazolidinediones (TZDs), are used clinically to treat type 2 diabetes due to their insulin-sensitizing effects. These drugs work by binding to and activating PPAR gamma, which in turn leads to the upregulation of genes involved in glucose uptake and metabolism in adipose tissue and skeletal muscle.

In summary, PPAR gamma is a nuclear receptor protein that regulates gene expression related to adipogenesis, lipid metabolism, insulin sensitivity, and glucose homeostasis. Its activation has therapeutic implications for the treatment of type 2 diabetes and other metabolic disorders.

Complementary DNA (cDNA) is a type of DNA that is synthesized from a single-stranded RNA molecule through the process of reverse transcription. In this process, the enzyme reverse transcriptase uses an RNA molecule as a template to synthesize a complementary DNA strand. The resulting cDNA is therefore complementary to the original RNA molecule and is a copy of its coding sequence, but it does not contain non-coding regions such as introns that are present in genomic DNA.

Complementary DNA is often used in molecular biology research to study gene expression, protein function, and other genetic phenomena. For example, cDNA can be used to create cDNA libraries, which are collections of cloned cDNA fragments that represent the expressed genes in a particular cell type or tissue. These libraries can then be screened for specific genes or gene products of interest. Additionally, cDNA can be used to produce recombinant proteins in heterologous expression systems, allowing researchers to study the structure and function of proteins that may be difficult to express or purify from their native sources.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Sterol 14-demethylase is an enzyme that plays a crucial role in the biosynthesis of sterols, particularly ergosterol in fungi and cholesterol in animals. This enzyme is classified as a cytochrome P450 (CYP) enzyme and is located in the endoplasmic reticulum.

The function of sterol 14-demethylase is to remove methyl groups from the sterol molecule at the 14th position, which is a necessary step in the biosynthesis of ergosterol or cholesterol. Inhibition of this enzyme can disrupt the normal functioning of cell membranes and lead to various physiological changes, including impaired growth and development.

Sterol 14-demethylase inhibitors (SDIs) are a class of antifungal drugs that target this enzyme and are used to treat fungal infections. Examples of SDIs include fluconazole, itraconazole, and ketoconazole. These drugs work by binding to the heme group of the enzyme and inhibiting its activity, leading to the accumulation of toxic sterol intermediates and disruption of fungal cell membranes.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

Dietary fats, also known as fatty acids, are a major nutrient that the body needs for energy and various functions. They are an essential component of cell membranes and hormones, and they help the body absorb certain vitamins. There are several types of dietary fats:

1. Saturated fats: These are typically solid at room temperature and are found in animal products such as meat, butter, and cheese, as well as tropical oils like coconut and palm oil. Consuming a high amount of saturated fats can raise levels of unhealthy LDL cholesterol and increase the risk of heart disease.
2. Unsaturated fats: These are typically liquid at room temperature and can be further divided into monounsaturated and polyunsaturated fats. Monounsaturated fats, found in foods such as olive oil, avocados, and nuts, can help lower levels of unhealthy LDL cholesterol while maintaining levels of healthy HDL cholesterol. Polyunsaturated fats, found in foods such as fatty fish, flaxseeds, and walnuts, have similar effects on cholesterol levels and also provide essential omega-3 and omega-6 fatty acids that the body cannot produce on its own.
3. Trans fats: These are unsaturated fats that have been chemically modified to be solid at room temperature. They are often found in processed foods such as baked goods, fried foods, and snack foods. Consuming trans fats can raise levels of unhealthy LDL cholesterol and lower levels of healthy HDL cholesterol, increasing the risk of heart disease.

It is recommended to limit intake of saturated and trans fats and to consume more unsaturated fats as part of a healthy diet.

Anticholesteremic agents are a class of medications that are used to lower the levels of cholesterol and other fats called lipids in the blood. These medications work by reducing the production of cholesterol in the body, increasing the removal of cholesterol from the bloodstream, or preventing the absorption of cholesterol in the digestive tract.

There are several types of anticholesteremic agents, including:

1. Statins: These medications work by blocking a liver enzyme that is necessary for the production of cholesterol. Examples of statins include atorvastatin, simvastatin, and rosuvastatin.
2. Bile acid sequestrants: These medications bind to bile acids in the digestive tract and prevent them from being reabsorbed into the bloodstream. This causes the liver to produce more bile acids, which in turn lowers cholesterol levels. Examples of bile acid sequestrants include cholestyramine and colesevelam.
3. Nicotinic acid: Also known as niacin, this medication works by reducing the production of very low-density lipoproteins (VLDL) in the liver, which are a major source of bad cholesterol.
4. Fibrates: These medications work by increasing the removal of cholesterol from the bloodstream and reducing the production of VLDL in the liver. Examples of fibrates include gemfibrozil and fenofibrate.
5. PCSK9 inhibitors: These are a newer class of medications that work by blocking the action of a protein called PCSK9, which helps regulate the amount of cholesterol in the blood. By blocking PCSK9, these medications increase the number of LDL receptors on the surface of liver cells, which leads to increased removal of LDL from the bloodstream.

Anticholesteremic agents are often prescribed for people who have high cholesterol levels and are at risk for heart disease or stroke. By lowering cholesterol levels, these medications can help reduce the risk of heart attack, stroke, and other cardiovascular events.

Lipoproteins are complex particles composed of multiple proteins and lipids (fats) that play a crucial role in the transport and metabolism of fat molecules in the body. They consist of an outer shell of phospholipids, free cholesterols, and apolipoproteins, enclosing a core of triglycerides and cholesteryl esters.

There are several types of lipoproteins, including:

1. Chylomicrons: These are the largest lipoproteins and are responsible for transporting dietary lipids from the intestines to other parts of the body.
2. Very-low-density lipoproteins (VLDL): Produced by the liver, VLDL particles carry triglycerides to peripheral tissues for energy storage or use.
3. Low-density lipoproteins (LDL): Often referred to as "bad cholesterol," LDL particles transport cholesterol from the liver to cells throughout the body. High levels of LDL in the blood can lead to plaque buildup in artery walls and increase the risk of heart disease.
4. High-density lipoproteins (HDL): Known as "good cholesterol," HDL particles help remove excess cholesterol from cells and transport it back to the liver for excretion or recycling. Higher levels of HDL are associated with a lower risk of heart disease.

Understanding lipoproteins and their roles in the body is essential for assessing cardiovascular health and managing risks related to heart disease and stroke.

DNA footprinting is a laboratory technique used to identify specific DNA-protein interactions and map the binding sites of proteins on a DNA molecule. This technique involves the use of enzymes or chemicals that can cleave the DNA strand, but are prevented from doing so when a protein is bound to the DNA. By comparing the pattern of cuts in the presence and absence of the protein, researchers can identify the regions of the DNA where the protein binds.

The process typically involves treating the DNA-protein complex with a chemical or enzymatic agent that cleaves the DNA at specific sequences or sites. After the reaction is stopped, the DNA is separated into single strands and analyzed using techniques such as gel electrophoresis to visualize the pattern of cuts. The regions of the DNA where protein binding has occurred are protected from cleavage and appear as gaps or "footprints" in the pattern of cuts.

DNA footprinting is a valuable tool for studying gene regulation, as it can provide insights into how proteins interact with specific DNA sequences to control gene expression. It can also be used to study protein-DNA interactions involved in processes such as DNA replication, repair, and recombination.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Leptin is a hormone primarily produced and released by adipocytes, which are the fat cells in our body. It plays a crucial role in regulating energy balance and appetite by sending signals to the brain when the body has had enough food. This helps control body weight by suppressing hunger and increasing energy expenditure. Leptin also influences various metabolic processes, including glucose homeostasis, neuroendocrine function, and immune response. Defects in leptin signaling can lead to obesity and other metabolic disorders.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Skeletal muscle, also known as striated or voluntary muscle, is a type of muscle that is attached to bones by tendons or aponeuroses and functions to produce movements and support the posture of the body. It is composed of long, multinucleated fibers that are arranged in parallel bundles and are characterized by alternating light and dark bands, giving them a striped appearance under a microscope. Skeletal muscle is under voluntary control, meaning that it is consciously activated through signals from the nervous system. It is responsible for activities such as walking, running, jumping, and lifting objects.

Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.

In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.

Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.

Regulator genes are a type of gene that regulates the activity of other genes in an organism. They do not code for a specific protein product but instead control the expression of other genes by producing regulatory proteins such as transcription factors, repressors, or enhancers. These regulatory proteins bind to specific DNA sequences near the target genes and either promote or inhibit their transcription into mRNA. This allows regulator genes to play a crucial role in coordinating complex biological processes, including development, differentiation, metabolism, and response to environmental stimuli.

There are several types of regulator genes, including:

1. Constitutive regulators: These genes are always active and produce regulatory proteins that control the expression of other genes in a consistent manner.
2. Inducible regulators: These genes respond to specific signals or environmental stimuli by producing regulatory proteins that modulate the expression of target genes.
3. Negative regulators: These genes produce repressor proteins that bind to DNA and inhibit the transcription of target genes, thereby reducing their expression.
4. Positive regulators: These genes produce activator proteins that bind to DNA and promote the transcription of target genes, thereby increasing their expression.
5. Master regulators: These genes control the expression of multiple downstream target genes involved in specific biological processes or developmental pathways.

Regulator genes are essential for maintaining proper gene expression patterns and ensuring normal cellular function. Mutations in regulator genes can lead to various diseases, including cancer, developmental disorders, and metabolic dysfunctions.

A plasmid is a small, circular, double-stranded DNA molecule that is separate from the chromosomal DNA of a bacterium or other organism. Plasmids are typically not essential for the survival of the organism, but they can confer beneficial traits such as antibiotic resistance or the ability to degrade certain types of pollutants.

Plasmids are capable of replicating independently of the chromosomal DNA and can be transferred between bacteria through a process called conjugation. They often contain genes that provide resistance to antibiotics, heavy metals, and other environmental stressors. Plasmids have also been engineered for use in molecular biology as cloning vectors, allowing scientists to replicate and manipulate specific DNA sequences.

Plasmids are important tools in genetic engineering and biotechnology because they can be easily manipulated and transferred between organisms. They have been used to produce vaccines, diagnostic tests, and genetically modified organisms (GMOs) for various applications, including agriculture, medicine, and industry.

A diet, in medical terms, refers to the planned and regular consumption of food and drinks. It is a balanced selection of nutrient-rich foods that an individual eats on a daily or periodic basis to meet their energy needs and maintain good health. A well-balanced diet typically includes a variety of fruits, vegetables, whole grains, lean proteins, and low-fat dairy products.

A diet may also be prescribed for therapeutic purposes, such as in the management of certain medical conditions like diabetes, hypertension, or obesity. In these cases, a healthcare professional may recommend specific restrictions or modifications to an individual's regular diet to help manage their condition and improve their overall health.

It is important to note that a healthy and balanced diet should be tailored to an individual's age, gender, body size, activity level, and any underlying medical conditions. Consulting with a healthcare professional, such as a registered dietitian or nutritionist, can help ensure that an individual's dietary needs are being met in a safe and effective way.

RNA-binding proteins (RBPs) are a class of proteins that selectively interact with RNA molecules to form ribonucleoprotein complexes. These proteins play crucial roles in the post-transcriptional regulation of gene expression, including pre-mRNA processing, mRNA stability, transport, localization, and translation. RBPs recognize specific RNA sequences or structures through their modular RNA-binding domains, which can be highly degenerate and allow for the recognition of a wide range of RNA targets. The interaction between RBPs and RNA is often dynamic and can be regulated by various post-translational modifications of the proteins or by environmental stimuli, allowing for fine-tuning of gene expression in response to changing cellular needs. Dysregulation of RBP function has been implicated in various human diseases, including neurological disorders and cancer.

  • Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene. (wikipedia.org)
  • We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. (reading.ac.uk)
  • The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. (reading.ac.uk)
  • Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. (reading.ac.uk)
  • Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. (reading.ac.uk)
  • Western blot analysis of SREBP-2. (bdbiosciences.com)
  • Cell lysates were probed with Purified Mouse Anti-SREBP-2 (Cat. (bdbiosciences.com)
  • As apoptosis is induced, the SREBP-2 125 kDa precursor is cleaved to its ~70 kDa size. (bdbiosciences.com)
  • Human SREBP-2 aa. (bdbiosciences.com)
  • SREBP-1 and -2 (sterol-regulatory element binding proteins-1 and -2) are transcription factors which participate in the control of cholesterol homeostasis. (bdbiosciences.com)
  • SREBP proteins, which are attached to the endoplasmic reticulum and nuclear envelope, are proteolytically cleaved and thus activated in response to conditions of low cellular sterol. (bdbiosciences.com)
  • Upon activation of SREBP-1 or -2, a ~480-500 amino acid, N-terminal cleavage fragment of these proteins enters the nucleus and activates transcription of enzymes and other proteins required for cholesterol synthesis. (bdbiosciences.com)
  • SREBP proteins containing point mutations at caspase-3 cleavage sites (Asp460 in SREBP-1 and Asp468 in SREBP-2) do not become cleaved following induction of apoptosis, suggesting that SREBPs may play some role in apoptotic processes. (bdbiosciences.com)
  • However, sterol-regulated vs. apoptosis-associated cleavage of SREBP proteins appears to be independently regulated. (bdbiosciences.com)
  • On SDS-PAGE, sterol-regulated cleavage fragments of SREBP proteins migrate more slowly (i.e., higher molecular weight) than do staurosporin-induced fragments. (bdbiosciences.com)
  • Essential FA, mainly polyunsaturated fatty acids (PUFA), may modulate gene expression in diverse biological processes thought regulating transcription factors (TF), including peroxisome proliferator receptors (PPAR) , liver X receptors (LXR) , and sterol regulatory element-binding proteins ( SREBP ) 3 . (nature.com)
  • Sterol regulatory element binding protein (SREBP)-1 is a transcription factor with important roles in the control of fatty acid metabolism and adipogenesis. (diabetesjournals.org)
  • Out of the three isoforms present (SREBP-1a, SREBP-1c and SREBP-2), SREBP-2 has been implicated more directly in the synthesis of cholesterol during metabolism. (novusbio.com)
  • Similar to SREBP-1a and SREBP-1c, SREBP-2 acts by first binding to sterol regulatory DNA sequences, and subsequently up-regulating the synthesis of enzymes involved in sterol biosynthesis. (novusbio.com)
  • SREBP-2 is expressed in both the cytoplasm and nucleus on a subcellular level, depending on the state of the protein. (novusbio.com)
  • This interaction prevents the cleavage of SREBP-2, which results in the synthesis of cholesterol and uptake of LDL despite high levels of present sterols. (novusbio.com)
  • Transfection of HepG2 cells with sense or antisense miR-370 or miR-122 upregulated and downregulated, respectively, the transcription factor sterol-regulatory element binding protein 1c (SREBP-1c) and the enzymes diacylglycerol acyltransferase-2 (DGAT2), fatty acid synthase (FAS), and acyl-CoA carboxylase 1 (ACC1) that regulate fatty acid and triglyceride biosynthesis. (nih.gov)
  • Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/β-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. (nature.com)
  • This effect, in turn, results in the upregulation of SREBP-2 , which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. (nature.com)
  • Expression of sterol regulatory element binding protein 1 (SREBP-1), ATP-citrate lyase (ACL), fatty acid synthase (FAS), malic enzyme (ME), acetyl-CoA carboxylase (ACC), and stearoyl-CoA (?9) desaturase 1 (SCD1) genes in ad lib birds declined from their highest levels just prior to photo-stimulation to reduced levels as the birds came into and maintained egg production. (usda.gov)
  • Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. (thebiogrid.org)
  • In this model of stress-induced cell senescence using DFO and H 2 O 2 , the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. (koreamed.org)
  • By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. (frontiersin.org)
  • 2007). Suppression of the genes, which are involved in lipogenesis (ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA-desaturase 1 or sterol regulatory element-binding protein 1(SREBP-1)), reduced proliferation and survival of hepatic carcinoma cells (Calvisi et al. (webmedcentral.com)
  • Using RNA sequencing and gene set enrichment analysis (GSEA), Set7 inhibitors upregulated the expression of genes involved in the control of cholesterol Sterol Regulatory Element-Binding Proteins (SREBP), cholesterol and fatty acyl biosynthesis. (edu.au)
  • Sterol regulatory element-binding proteins (SREBPs) compose a family of transcriptional factors that regulate the expression of various genes required for the synthesis of phospholipids, fatty acids, and cholesterol. (novusbio.com)
  • Brown, MS & Goldstein, JL 1998, ' Seventeenth Marabou Symposium on Diet and Genetic Interactions: Sterol regulatory element binding proteins (SREBPs): Controllers of lipid synthesis and cellular uptake ', Nutrition Reviews , vol. 56, no. 2 II, pp. (elsevierpure.com)
  • Exposure of isolated human adipocytes to tumor necrosis factor-α (TNF-α) produced a marked and specific decrease in the mRNA encoding the SREBP1c isoform and completely blocked the insulin-induced cleavage of SREBP1 protein. (diabetesjournals.org)
  • Upon binding to its receptor, insulin activates a cascade of intracellular signaling events. (alliedacademies.org)
  • Insulin signaling pathway activates phosphatidylinositol 3-kinase (PI3K), which phosphorylates and activates Akt (also known as protein kinase B). Akt regulates glucose transport by promoting the translocation of glucose transporters, such as GLUT4, to the plasma membrane. (alliedacademies.org)
  • In the poster section, Joanna Shisler (University of Illinois at Urbana-Champaign [UIUC], Urbana) reported that the modified virus, Ankara, activates nuclear factor κB through the mitogen-activated protein kinase, extracellular signal–regulated kinase (MEK)/extracellular signal–regulated kinase (ERK) pathway, possibly facilitating the host immune response. (cdc.gov)
  • Methionine is an essential amino acid, that affects the metabolism of protein, lipid and glucose. (researchsquare.com)
  • Cholesterol is a sterol, a type of lipid molecule composed of a complex structure of four fused hydrocarbon rings. (biochemden.com)
  • Because levels of transcription factor CCAAT/enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and lipoprotein lipase are also increased, lipid transport into cells and fatty acid synthesis within cells is increased ( 8 - 15 ). (cdc.gov)
  • This gene encodes a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes. (wikipedia.org)
  • Hepatic expression of fatty acid binding protein (FABP), very low density apolipoprotein II (ApoVLDL-II) and apolipoprotein B (ApoB) genes increased in both ad lib and restricted breeders following photo-stimulation, whereas apolipoprotein A1 (ApoA1) gene expression declined in both groups. (usda.gov)
  • Transcriptome profiling by RNA sequencing and GSEA studies showed PFI-2 and cyproheptadine hydrochloride can attenuate TNF-α induced gene expression. (edu.au)
  • Having shown that pharmacological inhibition of Set7 activity attenuates TNF-α driven gene expression, we proposed that PFI-2 and cyproheptadine hydrochloride could suppress TNF-α induced cytokine release. (edu.au)
  • The discovery of the NPC1 gene by Carstea et al[1] in 1997 has stimulated much research in Niemann-Pick disease, the NPC1 gene product, sterol trafficking, and gene therapy in animal models. (medscape.com)
  • Hence, evidenced the blocking of phosphatidylinositol 3-kinase/protein kinase B signaling pathway. (ijpsonline.com)
  • It induced apoptosis, suppressed cell migration and invasion, blocked cell cycle and phosphatidylinositol 3-kinase/ protein kinase B signaling pathway. (ijpsonline.com)
  • High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. (biomedcentral.com)
  • BCL2 proteins are described as 'crucial regulators of apoptosis' (PMID:15868100)and the intrinsic apoptosis pathway is initiated by the release of mitochondrial cytochrome c into the cytoplasm, which results in the activation of caspases (15102863) - help in generating a defintion for intrinsic apoptosis? (geneontology.org)
  • In adipocytes, the sterol regulatory element binding protein pathway is increased, resulting in increases in levels of sterol regulatory element binding protein 1 and fatty acid synthase. (cdc.gov)
  • Therefore, it is important to understand the genetic regulatory mechanisms for controlling fat metabolism in poultry during rearing and breeding periods of production. (usda.gov)
  • We also demonstrate that HLCs express proteins essential for lipoprotein metabolism, secrete authentic VLDL particles, and respond to metabolic perturbations, supporting their value for modeling hepatosteatosis and VLDL metabolism in vitro. (columbia.edu)
  • Conclusion: In the present study, RBSO appeared to improve sugar metabolism as evidenced by reduction in FBS, PPBS and HbA1c in type-2 diabetic patients. (longdom.org)
  • These data suggest that Treg control of Teff metabolism regulates inflammation differentially in prediabetes compared with type 2 diabetes. (diabetesjournals.org)
  • In response to the elevated glutamate in the liver, the expression of metabotropic glutamate receptor 5 (mGluR5) is up-regulated in hepatic stellate cells (HSCs) along with enhanced production of 2-arachidonoylglycerol, which in turn stimulates cannabinoid receptor 1 (CB 1 R) on neighboring hepatocytes to increase de novo lipogenesis. (e-cmh.org)
  • Interestingly, although the increased expression of CYP2E1-mediated xCT and ROS generation are mainly observed at the perivenous area (zone 3), fat accumulation is mostly detected at hepatic zone 2. (e-cmh.org)
  • In addition, muscular PEPCK and glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% methionine. (researchsquare.com)
  • A basic helix-loop-helix leucine zipper (bHLHZ) transcription factor and proto-oncogene protein that functions in cell growth and proliferation. (bvsalud.org)
  • Jurkat (ATCC TIB-152) cells were left untreated (lanes 1 & 2) or treated with 1 µM Staurosporin for 4 hours (lanes 3 & 4) to induce apoptosis. (bdbiosciences.com)
  • This revealed increased expression of B-cell lymphoma 2 associated X and reduced expression of B-cell lymphoma 2, indicating apoptosis induction by piperine. (ijpsonline.com)
  • does all activation of caspases require other proteins also involved in apoptosis - therefore shouldn't this term be a part of apoptosis? (geneontology.org)
  • how to decide whether a protein is involved in '+ve reg of apoptosis or induction ([GO:0006917])?emily. (geneontology.org)
  • Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. (koreamed.org)
  • We suggested a more plausible explanation based on the results of our recent study, which found that enhanced lipogenesis in response to expression of sterol regulatory element binding protein 1 (SREBP1, also known as SREBF1) is involved in the increase in the organellar mass observed in senescent cells [ 10 ]. (koreamed.org)
  • When cellular cholesterol levels are depleted, these genes are all transcribed in abundant amounts, and their transcription is repressed when sterols build up within the cell. (elsevierpure.com)
  • On the other hand, pharmacological inhibition of Set7 by PFI-2 and cyproheptadine hydrochloride reduced the expression of genes implicated in cell cycle and smooth muscle cell contraction. (edu.au)
  • Western blotting assay was implemented to check the levels of phosphatidylinositol 3-kinase and protein kinase B. Results revealed that piperine induced dose reliant cytotoxicity in MCF-7 human breast cancer cells. (ijpsonline.com)
  • Finally, Western blotting assay predicted constant expression of phosphatidylinositol 3-kinase and protein kinase B and reduced expression of phosphorylated phosphatidylinositol 3-kinase. (ijpsonline.com)
  • The protein levels of phospho-phosphatidylinositol 3-kinase, protein kinase B, phospho-eukaryotic initiation factor 4E binding protein-1 (p-4E-BP1), 4E-BP1 and ribosomal protein S6 kinase 1, in the liver of fish fed the 0.84% diet were higher than those in fish fed the 0.40% diet. (researchsquare.com)
  • AMP-Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. (alliedacademies.org)
  • We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H 2 O 2 . (koreamed.org)
  • A disparate array of plasma/serum markers provides evidence for chronic inflammation in prediabetes ( 2 , 3 ) that contrasts with our rich understanding of cellular sources of inflammation in human type 2 diabetes and animal models of insulin resistance (IR) ( 4 ). (diabetesjournals.org)
  • The sympathetic nervous system regulates this function through β-adrenergic stimulation of brown mature adipocytes' dissipation of energy in the form of heat mediated by mitochondrial uncoupling protein-1 (UCP-1) activation. (springer.com)
  • SREBF2 has been shown to interact with INSIG1 and CREB-binding protein. (wikipedia.org)
  • Obesity and its metabolic complications (e.g. type 2 diabetes, cardiometabolic disorders) contributing to the metabolic syndrome represent one of the most important public health problems, with societal and economic implications urging for new therapeutic strategies and effective social policies. (springer.com)
  • Type 2 Diabetes is associated with chronic hyperglycemia due to metabolic disorders caused by insulin resistance [ 1 ]. (longdom.org)
  • Obesity-associated prediabetes is a compromised metabolic state defined mainly by hyperglycemia that falls short of criteria for type 2 diabetes and is less likely to perpetuate complications like renal and cardiovascular diseases. (diabetesjournals.org)
  • RNA-sequencing and qPCR validation reveal that the Sterol Regulatory Element Binding Protein 2 (SREBP2)-mediated transcriptional program regulating cholesterol synthesis is significantly increased in TM6SF2 KO iPSCs. (columbia.edu)
  • Inhibition of triacylglycerol (TAG) synthesis via diacylglycerol acyltransferase 2 (DGAT2) antisense oligonucleotides improves liver steatosis (Yamaguchi et al. (webmedcentral.com)
  • Cholesterol synthesis is a complex process involving a series of enzymatic reactions and regulatory steps in various cell organelles. (biochemden.com)
  • When activated, AMPK phosphorylates and inhibits enzymes involved in ATP-consuming processes, such as fatty acid synthesis (e.g., acetyl-CoA carboxylase, ACC) and protein synthesis (e.g., mammalian target of rapamycin, mTOR). (alliedacademies.org)
  • The Niemann-Pick group of diseases can be subclassified into two categories: (1) those with a primary deficiency in acid sphingomyelinase (ASM) activity (ie, types A and B) and (2) those with defective intracellular processing and transporting of low-density lipoprotein (LDL)-derived cholesterol (ie, type C). (medscape.com)
  • The formation of a complex then enables Lon to degrade free ribosomal proteins. (go.jp)
  • Certain very abundant ribosomal proteins can be the sacrificial substrates targeted for degradation at the onset of the downshift. (go.jp)
  • It has been known to interact and form a complex with the SCAP protein at the ER, in turn inhibiting interaction between SCAP and SEC24B. (novusbio.com)
  • The IgG-1C6 antibody may be used for western blot analysis (2 µg/ml) and immunoprecipitation (2 µg antibody/300-500 µg of total protein lysate). (bdbiosciences.com)
  • Western Blot: SREBP2 Antibody (1D2) [NBP1-54446] - Lane1: HEp-2 cells. (novusbio.com)
  • Its oils are rich sources of unsaturated fatty acids, such as monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids, which are previously associated with the prevention of health disorders because of their anti-inflammatory effects and cell membrane properties and structure 2 . (nature.com)
  • Of note, circulating free fatty acids may also function as endogenous ligands for TLR binding as so-called danger associated molecular patterns, DAMPs. (frontiersin.org)
  • U-937 human histiocytic lymphoma cells (ATCC CRL-1593) or HeLa human cervical carcinoma cells (ATCC CCL-2) are recommended as additional positive controls. (bdbiosciences.com)
  • Sodium azide may be removed by washing stained cells or plate-bound antibody or dialyzing soluble antibody in sodium azide-free buffer. (bdbiosciences.com)
  • Lane 2: MCF-7 cells. (novusbio.com)
  • To solve this dilemma, cells must use their own proteins as sources of amino acids in response to the nutritional downshift. (go.jp)
  • BC comprises of variant subtypes and those subtypes arise from basal progenitor or luminal progenitor cells undergoing different genetic mutations[ 2 ]. (ijpsonline.com)
  • In addition to loss of replicative capacity, senescent cells display alterations in morphology, mass, and the dynamics of subcellular organelles [ 2 - 4 ]. (koreamed.org)
  • In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. (bvsalud.org)
  • Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system. (bvsalud.org)
  • Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. (bvsalud.org)
  • Regulatory T cells (Treg) control mitochondrial function and cytokine production by CD4 + effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. (diabetesjournals.org)
  • Set7 is also associated with regulation of different non-histone proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). (edu.au)
  • In this project, HMEC-1 cells were used to assess the Set7 inhibitors, PFI-2 and cyproheptadine hydrochloride mediated regulation under basal conditions and during TNF-α induced inflammation. (edu.au)
  • The World Health Organization reported that A significant number of patients with type 2 diabetes die from cardiovascular diseases [ 3 ]. (longdom.org)
  • Chronic alcohol intake leads to a broad spectrum of alcoholic liver disease (ALD) such as simple steatosis, steatohepatitis, hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma [ 2 , 4 ]. (e-cmh.org)
  • Diabetes Metab J. 2023;47(2):153-163. (e-dmj.org)
  • Samples of liver and abdominal fat pad were collected at the following times: 1) just prior to photo-stimulation, 2) after photo-stimulation at first egg, and 3) through peak egg production. (usda.gov)
  • Given the pivotal role that lipoproteins play at the juncture of these two conditions, researchers hypothesize that the ER-membrane spanning TM6SF2 protein regulates the degree of lipidation of VLDL particles synthesized in the liver. (columbia.edu)
  • Sterol regulatory element-binding protein 1 depends on insulin for fatty acid and cholesterol production. (testosteronejunkie.com)
  • The increase in the incidence of type 2 diabetes is largely attributable to lifestyle changes including diet, increasing age and sedentary life [ 2 ]. (longdom.org)
  • Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two growing and related diseases in general population and particularly in elderly people. (hindawi.com)
  • However, in the context of sustained obesity, WAT undergoes fibro-inflammation, which compromises its functionality, contributing to increased risk of type 2 diabetes and cardiovascular diseases. (springer.com)
  • PMID:14996496, table 1 provides links to papers that describe subcellular location of many pro- and anti-apoptotic proteins. (geneontology.org)
  • Transcript levels of SREBP1c, the most abundant isoform in adipose tissue, were significantly decreased in the subcutaneous adipose tissue of obese normoglycemic and type 2 diabetic subjects compared with that of nonobese normoglycemic control subjects. (diabetesjournals.org)
  • Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. (biomedcentral.com)
  • Cytochrome c then forms a multi-protein complex known as the 'apoptosome' and initiates activation of the caspase cascade through caspase 9. (geneontology.org)
  • Simultaneously detect the levels of these cytokines, chemokines, and acute phase proteins in a single sample. (rndsystems.com)
  • Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection. (shimamlab.info)
  • Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two related and growing health care problems [ 1 , 2 ], with an increasing trend in elderly people [ 3 ]. (hindawi.com)
  • In skeletal muscle, SREBP1 expression was significantly reduced in type 2 diabetic subjects but not in obese subjects. (diabetesjournals.org)
  • The specific reduction in the SREBP1c isoform seen in the adipose tissue of obese and type 2 diabetic subjects can be recapitulated ex vivo by TNF-α, suggesting a possible mechanism for this association. (diabetesjournals.org)
  • These remain largely nonactionable and contrast with our rich understanding of inflammation in human type 2 diabetes. (diabetesjournals.org)
  • The very large pool of people with prediabetes are at high risk for type 2 diabetes, although prediabetes is very reversible through lifestyle changes, while medications like metformin delay progression to type 2 diabetes ( 1 ). (diabetesjournals.org)
  • A better understanding of prediabetes is an important goal that could prevent a considerable number of type 2 diabetes cases. (diabetesjournals.org)
  • Mechanistically, QL-007 blocked the encapsidation of pgRNA and induced aberrant polymers assembly at concentrations ≥100 nM, while having no impact on the stability of core proteins. (bvsalud.org)

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