Endoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Unfolded Protein Response: A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.Transcription Factor CHOP: A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.Activating Transcription Factor 6: One of the BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTORS that is synthesized as a membrane-bound protein in the ENDOPLASMIC RETICULUM. In response to endoplasmic reticulum stress it translocates to the GOLGI APPARATUS. It is activated by PROTEASES and then moves to the CELL NUCLEUS to regulate GENETIC TRANSCRIPTION of GENES involved in the unfolded protein response.Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Stress, Physiological: The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.Activating Transcription Factor 4: An activating transcription factor that regulates the expression of a variety of GENES involved in amino acid metabolism and transport. It also interacts with HTLV-I transactivator protein.Thapsigargin: A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.Taurochenodeoxycholic Acid: A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic.Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.Endoplasmic Reticulum, Rough: A type of endoplasmic reticulum (ER) where polyribosomes are present on the cytoplasmic surfaces of the ER membranes. This form of ER is prominent in cells specialized for protein secretion and its principal function is to segregate proteins destined for export or intracellular utilization.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.PhenylbutyrateseIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.Eukaryotic Initiation Factor-2: Eukaryotic initiation factor of protein synthesis. In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. As initiation proceeds, eIF-2 forms a ternary complex with Met-tRNAi and GTP.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Endoplasmic Reticulum, Smooth: A type of endoplasmic reticulum lacking associated ribosomes on the membrane surface. It exhibits a wide range of specialized metabolic functions including supplying enzymes for steroid synthesis, detoxification, and glycogen breakdown. In muscle cells, smooth endoplasmic reticulum is called SARCOPLASMIC RETICULUM.Membrane Proteins: 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.Sarcoplasmic Reticulum Calcium-Transporting ATPases: Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.Endoribonucleases: A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Signal Transduction: 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.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Caspases, Initiator: A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.CinnamatesBrefeldin A: A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cells, Cultured: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Calnexin: A lectin found in ENDOPLASMIC RETICULUM membranes that binds to specific N-linked OLIGOSACCHARIDES found on newly synthesized proteins. It may play role in PROTEIN FOLDING or retention and degradation of misfolded proteins in the endoplasmic reticulum.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Blotting, Western: 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.Protein Disulfide-Isomerases: Sulfur-sulfur bond isomerases that catalyze the rearrangement of disulfide bonds within proteins during folding. Specific protein disulfide-isomerase isoenzymes also occur as subunits of PROCOLLAGEN-PROLINE DIOXYGENASE.Insulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Molecular Sequence Data: 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.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.HSP70 Heat-Shock Proteins: A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.Gene Expression Regulation: 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.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Mice, Inbred C57BLMutation: 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.Amino Acid Sequence: 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.Protein Processing, Post-Translational: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Calcium-Transporting ATPases: Cation-transporting proteins that utilize the energy of ATP hydrolysis for the transport of CALCIUM. They differ from CALCIUM CHANNELS which allow calcium to pass through a membrane without the use of energy.Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.RNA, Messenger: 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.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Up-Regulation: A positive 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.Mice, Knockout: 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.Secretory Pathway: A series of sequential intracellular steps involved in the transport of proteins (such as hormones and enzymes) from the site of synthesis to outside the cell. The pathway involves membrane-bound compartments through which the newly synthesized proteins undergo POST-TRANSLATIONAL MODIFICATIONS, packaging, storage, or transportation to the PLASMA MEMBRANE for secretion.CCAAT-Enhancer-Binding Proteins: 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.Transfection: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.DNA-Binding Proteins: 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.Microsomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Basic-Leucine Zipper Transcription Factors: A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reverse Transcriptase Polymerase Chain Reaction: 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.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Protein Binding: 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.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols.Activating Transcription Factor 3: An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Aspartate-Ammonia Ligase: An enzyme that catalyzes the formation of asparagine from ammonia and aspartic acid, in the presence of ATP. EC 6.3.1.1.Boronic Acids: Inorganic or organic compounds that contain the basic structure RB(OH)2.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Pulmonary Surfactant-Associated Protein C: A pulmonary surfactant associated protein that plays a role in alveolar stability by lowering the surface tension at the air-liquid interface. It is a membrane-bound protein that constitutes 1-2% of the pulmonary surfactant mass. Pulmonary surfactant-associated protein C is one of the most hydrophobic peptides yet isolated and contains an alpha-helical domain with a central poly-valine segment that binds to phospholipid bilayers.PyrazinesEnzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Protein Sorting Signals: Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Proteasome Inhibitors: Compounds that inhibit the function or proteolytic action of the PROTEASOME.COP-Coated Vesicles: TRANSPORT VESICLES formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of COP (coat protein complex) proteins, either COPI or COPII. COPI coated vesicles transport backwards from the cisternae of the GOLGI APPARATUS to the rough endoplasmic reticulum (ENDOPLASMIC RETICULUM, ROUGH), while COPII coated vesicles transport forward from the rough endoplasmic reticulum to the Golgi apparatus.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Fatty Liver: 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.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.ButylaminesFluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Rats, Transgenic: Laboratory rats that have been produced from a genetically manipulated rat EGG or rat EMBRYO, MAMMALIAN. They contain genes from another species.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Diet, High-Fat: Consumption of excessive DIETARY FATS.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Glucose: 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.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Palmitates: Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Down-Regulation: 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.Rats, Sprague-Dawley: 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.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.Cell Fractionation: Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Inositol 1,4,5-Trisphosphate Receptors: Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM.Cholagogues and Choleretics: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Insulin: 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).Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Vesicular Transport Proteins: A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Houttuynia: A plant genus of the family SAURURACEAE. Members contain aristolactams.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Cell Compartmentation: A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.HSP40 Heat-Shock Proteins: A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.Muscular Disorders, Atrophic: Disorders characterized by an abnormal reduction in muscle volume due to a decrease in the size or number of muscle fibers. Atrophy may result from diseases intrinsic to muscle tissue (e.g., MUSCULAR DYSTROPHY) or secondary to PERIPHERAL NERVOUS SYSTEM DISEASES that impair innervation to muscle tissue (e.g., MUSCULAR ATROPHY, SPINAL).Endoplasmic Reticulum-Associated Degradation: A degradation process whereby incorrectly folded proteins are selectively transported out of the ENDOPLASMIC RETICULUM and into the CYTOSOL. The misfolded proteins are subsequently ubiquitinated and degraded by the PROTEASOME.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.MAP Kinase Kinase Kinase 5: A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Lafora Disease: A form of stimulus sensitive myoclonic epilepsy inherited as an autosomal recessive condition. The most common presenting feature is a single seizure in the second decade of life. This is followed by progressive myoclonus, myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, and severe motor and coordination impairments. Most affected individuals do not live past the age of 25 years. Concentric amyloid (Lafora) bodies are found in neurons, liver, skin, bone, and muscle (From Menkes, Textbook of Childhood Neurology, 5th ed, pp111-110)DNA Primers: 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.Cell Nucleus: 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)Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Activating Transcription Factors: Activating transcription factors were originally identified as DNA-BINDING PROTEINS that interact with early promoters from ADENOVIRUSES. They are a family of basic leucine zipper transcription factors that bind to the consensus site TGACGTCA of the cyclic AMP response element, and are closely related to CYCLIC AMP-RESPONSIVE DNA-BINDING PROTEIN.Mitogen-Activated Protein Kinase 8: A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.Anterior Horn Cells: MOTOR NEURONS in the anterior (ventral) horn of the SPINAL CORD which project to SKELETAL MUSCLES.Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.Kinetics: The rate dynamics in chemical or physical systems.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Acetylcysteine: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Plasmids: 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.CHO Cells: 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.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.Liver Diseases, Alcoholic: Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Response Elements: 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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.Protein Phosphatase 1: A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Promoter Regions, Genetic: 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.

*  Endoplasmic Reticulum Stress and Lipid Metabolism

Endoplasmic Reticulum Stress and Lipid Metabolism. Huiping Zhou,1,2 Kezhong Zhang,3,4 Sabina Janciauskiene,5 and Xiaokun Li6 ... "Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy ...
https://hindawi.com/journals/bri/2012/257528/citations/

*  HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway.

HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway.. ... P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these ... for 24h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein ... response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress ...
https://omicsonline.org/references/hmgb1-induces-an-inflammatory-response-in-endothelial-cells-via-the-ragedependent-endoplasmic-reticulum-stress-pathway-337018.html

*  Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal...

Harding H. P.,Ron D.. (Year: 2002). Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes51, S455- ... Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal ... Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal ... Hotamisligil G. S.. (Year: 2010). Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell140, 900- ...
biomedsearch.com/nih/Bile-acid-mediated-decrease-in/23264565.html

*  Down-regulation of miR-384-5p Attenuates Rotenone-induced Neurotoxicity in Dopaminergic SH-SY5Y Cells Through Inhibiting...

Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of ... 5p Attenuates Rotenone-induced Neurotoxicity in Dopaminergic SH-SY5Y Cells Through Inhibiting Endoplasmic Reticulum Stress. ... 5p Attenuates Rotenone-induced Neurotoxicity in Dopaminergic SH-SY5Y Cells Through Inhibiting Endoplasmic Reticulum Stress ... 5p Attenuates Rotenone-induced Neurotoxicity in Dopaminergic SH-SY5Y Cells Through Inhibiting Endoplasmic Reticulum Stress ...
ajpcell.physiology.org/content/early/2016/02/09/ajpcell.00226.2015

*  Endoplasmic reticulum stress and intestinal inflammation - Blumberg Richard

... stress is an ancient conserved mechanism that allows cells, especially those with significant secretory function such as ... Endoplasmic reticulum stress and intestinal inflammation Richard, Blumberg S. Brigham and Women's Hospital, Boston, MA, United ... Endoplasmic reticulum stress and intestinal inflammation. Blumberg, Richard S. / Brigham and Women's Hospital. $647,667. ... Endoplasmic reticulum stress and intestinal inflammation. Blumberg, Richard S. / Brigham and Women's Hospital. $515,237. ...
grantome.com/grant/NIH/R01-DK088199-05

*  Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery - Research Collection

Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery. * Mendeley ...
https://research-collection.ethz.ch/handle/20.500.11850/122911

*  Dr Kelly Kiejda / Staff Profile / The University of Newcastle, Australia

The microRNA signature of endoplasmic reticulum stress in melanoma$10,000 Funding body: Calvary Mater Newcastle ...
https://newcastle.edu.au/profile/kelly-kiejda?group=g

*  Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity. ...

... revealed the endoplasmic reticulum (ER) stress/translational initiation signaling and nuclear factor-erythroid 2 (NF-E2)- ... The ER stress induced was primarily related to protein kinase R-like ER kinase (PERK) and activating transcription factor 4 ( ... Targeted RNA interference studies revealed that whereas ER stress signaling through inositol-requiring enzyme 1α (IRE1α) and ... Whereas inhibition of the Nrf2-dependent adaptive oxidative stress response enhanced the drug/TNFα cytotoxicity, Nrf2 signaling ...
https://semanticscholar.org/paper/Drug-induced-endoplasmic-reticulum-and-oxidative-s-Fredriksson-Wink/b3b29132d51c266a27c0a3fadc78a3f2a2c8c7d2

*  Ebook 978-9048136957 Heterogenized Homogeneous Catalysts for Fine Chemicals Production: Materials

Ebook 978-9400743502 Endoplasmic Reticulum Stress in Health and Disease. digitalbooks365 * $98.42 ...
ecrater.com/p/27665388/ebook-978-9048136957-heterogenized-homogeneous-catalysts-for-fine

*  Luis B. Agellon | School of Human Nutrition - McGill University

Coping with endoplasmic reticulum stress in the cardiovascular system (PMID 23020580). Endoplasmic reticulum stress, genome ...
https://mcgill.ca/nutrition/staff/professors/agellon

*  ER stress shapes muscle | JCB

On page 555, Nakanishi et al. show that ER stress triggers apoptosis during muscle development. It is the ER stress pathway's first appearance in a nonpathological context.. As muscle precursor cells called myoblasts differentiate, they fuse into multinucleated myotubes. This process is accompanied by a considerable amount of apoptosis-up to 20% of the myoblasts die. The new results show that markers of the ER stress-signaling pathway are up-regulated during this process.. ER stress-induced apoptosis is preceded by the unfolded protein response (UPR), which up-regulates ER chaperones such as BiP. The authors found BiP and ER stress-specific caspase-12 in differentiating myoblasts, including the survivors. In dying myoblasts, death effector caspases such as caspase-9 and -3 were also activated. Survival versus death might depend on the relative amounts of caspases versus antiapoptotic proteins such as XIAPs. Apoptosis might ...
jcb.rupress.org/content/169/4/548.2

Endoplasmic Reticulum Stress in Beta Cells: Beta cells are heavily engaged in the synthesis and secretion of insulin. They are therefore particularly sensitive to endoplasmic reticulum (ER) stress and the subsequent unfolded protein response(UPR).Chaperone (protein): 250px|right|thumb|A top-view of the [[GroES/GroEL bacterial chaperone complex model]]Amino acid response: Amino acid response (AAR) is the mechanism triggered in mammalian cells by amino acid starvation.Taurochenodeoxycholic acidHeat shock protein: Heat shock proteins (HSP) are a family of proteins that are produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light, and during wound healing or tissue remodeling..Protein kinase R: Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by the EIF2AK2 gene.Knotted protein: Knotted proteins are proteins whose backbones entangle themselves in a knot. One can imagine pulling a protein chain from both termini, as though pulling a string from both ends.Sarcalumenin: Sarcalumenin is a protein that in humans is encoded by the SAR gene.CisternaHepatocyte: A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 70-85% of the liver's mass.Membrane protein: Membrane proteins are proteins that interact with biological membranes. They are one of the common types of protein along with soluble globular proteins, fibrous proteins, and disordered proteins.Mydicar: Mydicar is a genetically targeted enzyme replacement therapy being studied for use in patients with severe heart failure. It is designed to increase the level of SERCA2a, a sarcoplasmic endoplasmic reticulum calcium (Ca2+) ATPase found in the membrane of the sarcoplasmic reticulum (SR).Ribonuclease L: Ribonuclease L or RNase L (for latent), known sometimes as ribonuclease 4 or 2'-5' oligoadenylate synthetase-dependent ribonuclease — is an interferon (IFN)-induced ribonuclease which, upon activation, destroys all RNA within the cell (both cellular and viral). RNase L is an enzyme that in humans is encoded by the RNASEL gene.Calreticulin protein family: In molecular biology, the calreticulin protein family is a family of calcium-binding proteins. This family includes Calreticulin, Calnexin and Camlegin.Calcium signaling: Calcium ions are important for cellular signalling, as once they enter the cytosol of the cytoplasm they exert allosteric regulatory effects on many enzymes and proteins. Calcium can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.Calnexin: Calnexin (CNX) is a 67kDa integral protein (that appears variously as a 90kDa, 80kDa or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail.Autophagy: Autophagy (or autophagocytosis) (from the Greek auto-, "self" and phagein, "to eat"), is the natural, destructive mechanism that disassembles, through a regulated process, unnecessary or dysfunctional cellular components.KduI/IolB isomerase family: In molecular biology, the KduI/IolB isomerase family is a family of isomerase enzymes.Pituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.Coles PhillipsProteasome: Proteasomes are protein complexes inside all eukaryotes and archaea, and in some bacteria. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds.HSP60Glycosylation: Glycosylation (see also chemical glycosylation) is the reaction in which a carbohydrate, i.e.Necrobiology: Necrobiology comprises the life processes associated with morphological, biochemical, and molecular changes which predispose, precede, and accompany cell death, as well as the consequences and tissue response to cell death. The word is derived from the Greek νεκρό meaning "death", βìο meaning "life", and λόγος meaning "the study of".Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.KIAA0895L: Uncharacterized protein KIAA0895-like also known as LOC653319, is a protein that in humans is encoded by the KIAA0895L gene.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GIThiourea dioxideMature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Matrix model: == Mathematics and physics ==Mitochondrion: The mitochondrion (plural mitochondria) is a double membrane-bound organelle found in most eukaryotic cells. The word mitochondrion comes from the Greek , , i.RNA transfection: RNA transfection is the process of deliberately introducing RNA into a living cell. RNA can be purified from cells after lysis or synthesized from free nucleotides either chemically, or enzymatically using an RNA polymerase to transcribe a DNA template.Cell membraneSerine/threonine-specific protein kinaseDNA-binding proteinCaspase 12: Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18.Hyperphosphorylation: Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signalling mechanisms used by the cell to regulate mitosis.Calcium encodingLow-voltage electron microscope: Low-voltage electron microscope (LVEM) is an electron microscope which operates at accelerating voltages of a few kiloelectronvolts or less. While the low voltage electron microscopy technique will never replace conventional high voltage electron microscopes, it is quickly becoming appreciated for many different disciplines.Mediated transportTranslational regulation: Translational regulation refers to the control of the levels of protein synthesized from its mRNA. The corresponding mechanisms are primarily targeted on the control of ribosome recruitment on the initiation codon, but can also involve modulation of the elongation or termination of protein synthesis.Proximity ligation assay: Proximity ligation assay (in situ PLA) is a technology that extends the capabilities of traditional immunoassays to include direct detection of proteins, protein interactions and modifications with high specificity and sensitivity. Protein targets can be readily detected and localized with single molecule resolution and objectively quantified in unmodified cells and tissues.Mitochondrial ROS: Mitochondrial ROS (mtROS or mROS) are reactive oxygen species (ROS) that are produced by mitochondria. Generation of mitochondrial ROS mainly takes place at the electron transport chain located on the inner mitochondrial membrane during the process of oxidative phosphorylation (OXPHOS).Total internal reflection fluorescence microscope: A total internal reflection fluorescence microscope (TIRFM) is a type of microscope with which a thin region of a specimen, usually less than 200 nm can be observed.Boronic acidBRICHOS family: The BRICHOS family consists of a variety of proteins linked to major diseases, each containing a 100 amino acid BRICHOS domain that is thought to have a chaperone function.BortezomibGating signal: A gating signal is a digital signal or pulse (sometimes called a "trigger") that provides a time window so that a particular event or signal from among many will be selected and others will be eliminated or discarded.

(1/901) Autophagy in the model alga Chlamydomonas reinhardtii.

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(2/901) Functions for the cardiomyokine, MANF, in cardioprotection, hypertrophy and heart failure.

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(3/901) Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in leukocytes from elderly humans.

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(4/901) Crohn's disease: NOD2, autophagy and ER stress converge.

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(5/901) Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK.

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(6/901) Cyclic stretch-induced apoptosis in rat annulus fibrosus cells is mediated in part by endoplasmic reticulum stress through nitric oxide production.

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(7/901) Modeling retinal degeneration using patient-specific induced pluripotent stem cells.

 (+info)

(8/901) Endoplasmic reticulum stress in wake-active neurons progresses with aging.

 (+info)



PERK


  • Our results showed that incubation of endothelial cells with HMGB1 (0.01-1 μg/ml) for 24h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. (omicsonline.org)
  • Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. (omicsonline.org)
  • The ER stress induced was primarily related to protein kinase R-like ER kinase (PERK) and activating transcription factor 4 (ATF4) activation and subsequent expression of C/EBP homologous protein (CHOP), which was all independent of TNFα signaling. (semanticscholar.org)
  • Targeted RNA interference studies revealed that whereas ER stress signaling through inositol-requiring enzyme 1α (IRE1α) and activating transcription factor 6 (ATF6) acted cytoprotective, activation of the ER stress protein kinase PERK and subsequent expression of CHOP was pivotal for the onset of drug/TNFα-induced apoptosis. (semanticscholar.org)
  • ER stress is sensed by the ER stress transducers PERK, IRE1, and ATF6 that activate the unfolded protein response (UPR). (diabetesjournals.org)

IRE1


  • Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1α). (physiology.org)

induce


  • We, and others, have previously shown that FFAs induce endoplasmic reticulum (ER) stress in β-cells ( 13 - 16 ). (diabetesjournals.org)

protein


  • Through bioinformatics and the dual-luciferase reporter assay, miR-384-5p was found to directly target the 3'-UTR of glucose regulated protein 78 (GRP78), the master regulator of ER stress sensors. (physiology.org)
  • The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR-384-5p inhibitor. (physiology.org)
  • Endoplasmic reticulum (ER) stress is an ancient conserved mechanism that allows cells, especially those with significant secretory function such as intestinal epithelial cells (IEC), to cope with the emergence of misfolded or unfolded proteins within the ER through a mechanism called the Unfolded Protein Response (UPR). (grantome.com)
  • Earlier, we reported the role of the small co-chaperone protein p23 in preventing ER stress-induced cell death. (pubmedcentralcanada.ca)
  • We recently described the role of the small co-chaperone protein p23 (a 23-kD HSP90-associated chaperone protein) in ER stress-induced cell death. (pubmedcentralcanada.ca)
  • ER stress, defined as an imbalance between protein folding demand and ER capacity, leads to accumulation of misfolded proteins. (diabetesjournals.org)

pathways


  • Transcriptomics of the cell injury stress response pathways initiated by two hepatoxicants, diclofenac and carbamazepine, revealed the endoplasmic reticulum (ER) stress/translational initiation signaling and nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) antioxidant signaling as two major affected pathways, which was similar to that observed for the majority of ∼80 DILI compounds in primary human hepatocytes. (semanticscholar.org)

oxidative stress


  • Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity. (semanticscholar.org)
  • Whereas inhibition of the Nrf2-dependent adaptive oxidative stress response enhanced the drug/TNFα cytotoxicity, Nrf2 signaling did not affect CHOP expression. (semanticscholar.org)
  • Lycopene's innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. (mdpi.com)

antibody


  • While patients with severe AD did display a consistent reduction in p23 levels, our inability to observe p19 in mouse or human AD brain samples suggests that the usefulness of the p23 neo-epitope antibody is restricted to cells and primary neurons undergoing cellular stress. (pubmedcentralcanada.ca)

responses


  • The presence of misfolded proteins elicits cellular responses including an endoplasmic reticulum (ER) stress response that may protect cells against the toxic buildup of misfolded proteins. (pubmedcentralcanada.ca)
  • Misfolded proteins elicit cellular stress responses including an ER stress response that serves to protect cells against the accumulation of these toxic proteins. (pubmedcentralcanada.ca)

affects


  • XBP1 function within intestinal epithelial cells (IEC) is associated with endoplasmic reticulum (ER) stress and affects the two central determinants of inflammatory bowel disease (IBD) pathogenesis;the bacteria found in the gastro-intestinal tract and immune response to these bacteria itself. (grantome.com)

metabolic


  • Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. (biomedsearch.com)
  • The data point to cross talk between metabolic stress and candidate genes at the β-cell level. (diabetesjournals.org)

adaptive


  • Functional studies identified novel mediators of adaptive ER stress signaling. (diabetesjournals.org)

novel


  • Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway. (omicsonline.org)
  • Taken together, our results suggested that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD. (physiology.org)

inflammatory


  • HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway. (omicsonline.org)
  • The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. (omicsonline.org)
  • Given that ER stress is readily demonstrable in animal models of inflammatory bowel disease (IBD) and the human condition and that the XBP1 gene harbors polymorphisms that confer risk for the development of IBD, it is reasonable to propose that the host's ability to manage ER stress within the IEC that is caused by environmental factors including inflammation itself is an important issue in understanding IBD pathogenesis. (grantome.com)

XBP1


  • Deletion of the XBP1 gene specifically within IECs leads, uniquely, to spontaneous enteritis and sensitivity to colitis-inducing agents in association with increased ER stress, loss of Paneth and goblet cell function, an inability to manage luminal microbial challenges and a hypersensitivity of the IEC to signals emanating from bacterial and immune factors. (grantome.com)
  • 3) Define the environmental factors involved in the exacerbation or alleviation of inflammation associated with XBP1- deficiency by characterizing the microbiome of XBP1-deficient mice and the role of the microbiota in inducing spontaneous enteritis and susceptibility to colitis and establishing whether agents that reduce ER stress can abrogate the intestinal inflammation arising from XBP1-deficient epithelia. (grantome.com)
  • Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis of transcription factor binding sites in palmitate-modified transcripts revealed a role for PAX4, GATA, and the ER stress response regulators XBP1 and ATF6. (diabetesjournals.org)

apoptosis


  • In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. (physiology.org)

proteins


  • Thus, a critical question is whether p23 and/or p19 could serve as an in vivo marker for neurodegenerative diseases featuring misfolded proteins and cellular stress. (pubmedcentralcanada.ca)

liver


  • Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. (biomedsearch.com)

results


  • These results suggest that post-operative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress. (biomedsearch.com)

studies


  • Studies from multiple laboratories have identified the roles of several ER stress-induced cell death modulators and effectors. (pubmedcentralcanada.ca)

cell


  • Cell culture models were used to investigate interactions between bile acids and ER stress. (biomedsearch.com)
  • Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. (biomedsearch.com)
  • Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. (biomedsearch.com)
  • p23 undergoes caspase-dependent cleavage to yield a 19-kD product (p19), and mutation of this caspase cleavage site not only blocks the formation of the 19-kD product but also attenuates the ER stress-induced cell death process triggered by various stressors. (pubmedcentralcanada.ca)
  • These findings suggested that the presence of p19 may be an indication of cells undergoing some form of cellular stress leading to cell death and neurodegeneration. (pubmedcentralcanada.ca)