An epoxydodecadienamide isolated from several species, including ACREMONIUM, Acrocylindrum, and Helicoceras. It inhibits the biosynthesis of several lipids by interfering with enzyme function.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Substances that are recognized by the immune system and induce an immune reaction.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Substances elaborated by bacteria that have antigenic activity.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Sequential operating programs and data which instruct the functioning of a digital computer.
The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.
Software application for retrieving, presenting and traversing information resources on the World Wide Web.
Specific languages used to prepare computer programs.
Organized activities related to the storage, location, search, and retrieval of information.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.
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.
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.
Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.
Databases devoted to knowledge about specific genes and gene products.
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)
The transference of a part of or an entire liver from one human or animal to another.
Non-cadaveric providers of organs for transplant to related or non-related recipients.
Repair or renewal of hepatic tissue.
Progressive destruction or the absence of all or part of the extrahepatic BILE DUCTS, resulting in the complete obstruction of BILE flow. Usually, biliary atresia is found in infants and accounts for one third of the neonatal cholestatic JAUNDICE.
Excision of all or part of the liver. (Dorland, 28th ed)
The chilling of a tissue or organ during decreased BLOOD perfusion or in the absence of blood supply. Cold ischemia time during ORGAN TRANSPLANTATION begins when the organ is cooled with a cold perfusion solution after ORGAN PROCUREMENT surgery, and ends after the tissue reaches physiological temperature during implantation procedures.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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.
A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
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.
The sum of the weight of all the atoms in a molecule.
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.
Databases devoted to knowledge about specific chemicals.
Databases devoted to knowledge about PHARMACEUTICAL PRODUCTS.
A family of hexahydropyridines.
The symptom of paroxysmal pain consequent to MYOCARDIAL ISCHEMIA usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the MYOCARDIUM exceed that supplied by the CORONARY CIRCULATION.
The metabolism of drugs and their mechanisms of action.
The veins and arteries of the HEART.
Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
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.
Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
Detection and counting of scintillations produced in a fluorescent material by ionizing radiation.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.

Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase. (1/220)

In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA. The enzyme is a possible drug target for treatment of certain cancers and for tuberculosis. The crystal structure of the complex of the enzyme from Escherichia coli, and the fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic pocket formed at the dimer interface. Cerulenin is covalently attached to the active site cysteine through its C2 carbon atom. The fit of the inhibitor to the active site is not optimal, and there is thus room for improvement through structure based design.  (+info)

Monounsaturated but not polyunsaturated fatty acids are required for growth of the deep-sea bacterium Photobacterium profundum SS9 at high pressure and low temperature. (2/220)

There is considerable evidence correlating the production of increased proportions of membrane unsaturated fatty acids (UFAs) with bacterial growth at low temperatures or high pressures. In order to assess the importance of UFAs to microbial growth under these conditions, the effects of conditions altering UFA levels in the psychrotolerant piezophilic deep-sea bacterium Photobacterium profundum SS9 were investigated. The fatty acids produced by P. profundum SS9 grown at various temperatures and pressures were characterized, and differences in fatty acid composition as a function of phase growth, and between inner and outer membranes, were noted. P. profundum SS9 was found to exhibit enhanced proportions of both monounsaturated (MUFAs) and polyunsaturated (PUFAs) fatty acids when grown at a decreased temperature or elevated pressure. Treatment of cells with cerulenin inhibited MUFA but not PUFA synthesis and led to a decreased growth rate and yield at low temperature and high pressure. In addition, oleic acid-auxotrophic mutants were isolated. One of these mutants, strain EA3, was deficient in the production of MUFAs and was both low-temperature sensitive and high-pressure sensitive in the absence of exogenous 18:1 fatty acid. Another mutant, strain EA2, produced little MUFA but elevated levels of the PUFA species eicosapentaenoic acid (EPA; 20:5n-3). This mutant grew slowly but was not low-temperature sensitive or high-pressure sensitive. Finally, reverse genetics was employed to construct a mutant unable to produce EPA. This mutant, strain EA10, was also not low-temperature sensitive or high-pressure sensitive. The significance of these results to the understanding of the role of UFAs in growth under low-temperature or high-pressure conditions is discussed.  (+info)

Acylation stabilizes a protease-resistant conformation of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides. (3/220)

Protein acylation is an important way in which a number of proteins with a variety of functions are modified. The physiological role of the acylation of cellular proteins is still poorly understood. Covalent binding of fatty acids to nonintegral membrane proteins is thought to produce transient or permanent enhancement of the association of the polypeptide chains with biological membranes. In this paper, we investigate the functional role for the palmitoylation of an atypical membrane-bound protein, yeast protoporphyrinogen oxidase, which is the molecular target of diphenyl ether-type herbicides. Palmitoylation stabilizes an active heat- and protease-resistant conformation of the protein. Palmitoylation of protoporphyrinogen oxidase has been demonstrated to occur in vivo both in yeast cells and in a heterologous bacterial expression system, where it may be inhibited by cerulenin leading to the accumulation of degradation products of the protein. The thiol ester linking palmitoleic acid to the polypeptide chain was shown to be sensitive to hydrolysis by hydroxylamine and also by the widely used serine-protease inhibitor phenylmethylsulfonyl fluoride.  (+info)

Biosynthesis and elongation of short- and medium-chain-length fatty acids. (4/220)

Short- and medium-chain-length fatty acids (FAs) are important constituents of a wide array of natural products. Branched and straight short-chain-length FAs originate from branched chain amino acid metabolism, and serve as primers for elongation in FA synthase-like reactions. However, a recent model proposes that the one-carbon extension reactions that utilize 2-oxo-3-methylbutyric acid in leucine biosynthesis also catalyze a repetitive one-carbon elongation of short-chain primers to medium-chain-length FAs. The existence of such a mechanism would require a novel form of regulation to control carbon flux between amino acid and FA biosynthesis. A critical re-analysis of the data used to support this pathway fails to support the hypothesis for FA elongation by one-carbon extension cycles of alpha-ketoacids. Therefore, we tested the hypothesis experimentally using criteria that distinguish between one- and two-carbon elongation mechanisms: (a) isotopomer patterns in terminal carbon atom pairs of branched and straight FAs resulting from differential labeling with [(13)C]acetate; (b)(13)C]threonine labeling patterns in odd- and even chain length FAs; and (c) differential sensitivity of elongation reactions to inhibition by cerulenin. All three criteria indicated that biosynthesis of medium-chain length FAs is mediated primarily by FA synthase-like reactions.  (+info)

Activity of the phosphatidylcholine biosynthetic pathway modulates the distribution of fatty acids into glycerolipids in proliferating cells. (5/220)

PtdCho accumulation is a periodic, S phase-specific event that is modulated in part by cell cycle-dependent fluctuations in CTP:phosphocholine cytidylyltransferase (CCT) activity. A supply of fatty acids is essential to generate the diacylglycerol (DG) precursors for phosphatidylcholine (PtdCho) biosynthesis but it is not known whether the DG supply is also coupled to the cell cycle. Although the rate of fatty acid synthesis in a macrophage cell line was dramatically stimulated in response to the growth factor, CSF-1, it was not regulated by the cell cycle. Increased fatty acid synthesis correlated with elevated acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) steady-state mRNA levels. Cellular fatty acid synthesis was essential for membrane PL synthesis. Cerulenin inhibition of endogenous fatty acid synthesis also inhibited PtdCho synthesis, which was not relieved by exogenous fatty acids. Inhibition of CCT activity by the addition of lysophosphatidylcholine (lysoPtdCho) or temperature-shift of a conditionally defective CCT diverted newly synthesized DG to the TG pool where it accumulated. Enforced expression of CCT stimulated PtdCho biosynthesis and reduced TG synthesis. Thus, the cellular DG supply did not regulate PtdCho biosynthesis and CCT activity governs the partitioning of DG into either the PL or TG pools, thereby controlling both PtdCho and TG biosynthesis.  (+info)

Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. (6/220)

A biologically aggressive subset of human breast cancers and other malignancies is characterized by elevated fatty-acid synthase (FAS) enzyme expression, elevated fatty acid (FA) synthesis, and selective sensitivity to pharmacological inhibition of FAS activity by cerulenin or the novel compound C75. In this study, inhibition of FA synthesis at the physiologically regulated step of carboxylation of acetyl-CoA to malonyl-CoA by 5-(tetradecyloxy)-2-furoic acid (TOFA) was not cytotoxic to breast cancer cells in clonogenic assays. FAS inhibitors induced a rapid increase in intracellular malonyl-CoA to several fold above control levels, whereas TOFA reduced intracellular malonyl-CoA by 60%. Simultaneous exposure of breast cancer cells to TOFA and an FAS inhibitor resulted in significantly reduced cytotoxicity and apoptosis. Subcutaneous xenografts of MCF7 breast cancer cells in nude mice treated with C75 showed FA synthesis inhibition, apoptosis, and inhibition of tumor growth to less than 1/8 of control volumes, without comparable toxicity in normal tissues. The data suggest that differences in intermediary metabolism render tumor cells susceptible to toxic fluxes in malonyl-CoA, both in vitro and in vivo.  (+info)

Specialized fatty acid synthesis in African trypanosomes: myristate for GPI anchors. (7/220)

African trypanosomes, the cause of sleeping sickness, need massive amounts of myristate to remodel glycosyl phosphatidylinositol (GPI) anchors on their surface glycoproteins. However, it has been believed that the parasite is unable to synthesize any fatty acids, and myristate is not abundant in the hosts' bloodstreams. Thus, it has been unclear how trypanosomes meet their myristate requirement. Here we found that they could indeed synthesize fatty acids. The synthetic pathway was unique in that the major product, myristate, was preferentially incorporated into GPIs and not into other lipids. The antibiotic thiolactomycin inhibited myristate synthesis and killed the parasite, making this pathway a potential chemotherapeutic target.  (+info)

Structural modeling and site-directed mutagenesis of the actinorhodin beta-ketoacyl-acyl carrier protein synthase. (8/220)

A three-dimensional model of the Streptomyces coelicolor actinorhodin beta-ketoacyl synthase (Act KS) was constructed based on the X-ray crystal structure of the related Escherichia coli fatty acid synthase condensing enzyme beta-ketoacyl synthase II, revealing a similar catalytic active site organization in these two enzymes. The model was assessed by site-directed mutagenesis of five conserved amino acid residues in Act KS that are in close proximity to the Cys169 active site. Three substitutions completely abrogated polyketide biosynthesis, while two replacements resulted in significant reduction in polyketide production. (3)H-cerulenin labeling of the various Act KS mutant proteins demonstrated that none of the amino acid replacements affected the formation of the active site nucleophile.  (+info)

Cerulenin is an antibiotic that inhibits eukaryotic lipid and sterol synthesis and blocks lipid modification of proteins. The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. This antibiotic strongly inhibits the ability of accessory cells to present antigen to murine T-T hybrids. This effect is observed for multiple distinct antigens including L-glutamic acid60-L-alanine30-L-tyrosine10, bovine insulin, L-glutamic acid56-L-lysine35-L-phenylalanine9, and ovalbumen. Presentation by both macrophage and B lymphoblastoid cell lines is inhibited. The ability to effectively pulse these cells with antigen is inhibited but not the ability of these same cells to present antigen that they have previously processed. Furthermore, this inhibition is selective as it can occur without significant inhibition of the antigen-presenting cell protein or DNA synthesis. Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. By ...
5620 Fatty acid synthase (FAS) is a 250-270 kd cytosolic multifunctional polypeptide required for the conversion of dietary carbohydrates to fatty acids. While high levels of FAS expression compared to normal tissue have been observed in several cancers, including breast, prostate, colon and lung carcinoma, there is little information regarding gliomas. For the first time, we show high levels of FAS expression associated with glioma cell lines. Western blotting revealed higher FAS expression (4-20 fold increase) in U251, U138, NSB-19, and U373 human glioma cell lines and in C6 rat glioma cells compared to normal rat astrocytes. Cerulenin-mediated inhibition of lipid synthesis was determined using 14C labeled acetic acid. After labeling, total lipids were extracted and counted for 14C by scintillation counting. Endogenous fatty acid synthesis in cerulenin-treated glioma cells decreased by 49%, 49.7% and 51.1% at 2 hours in NSB-19, U251, and C6 cells, respectively. Cell cycle analysis, using flow ...
1 mCi quantities of [2-14C]-Acetic Acid, Sodium Salt, Specific Activity: 45-60mCi (1.66-2.22GBq)/mmol are available for your research. Application of [14C]Acetic Acid can be found in: migration in paddy soil-to-rice plant system after breakdown by microorganisms below the plow layer in geological disposal research, effects of cerulenin on the endogenous fatty acid synthetic activity in oral squamous cell carcinoma (OSCC), in vivo incorporation into goldfish liver lipids during ?-hexachlorocyclohexane exposure in aquatic toxicology, etc.. ...
1 mCi quantities of [1,2-14C]-Acetic Acid, Sodium Salt are available for your research. Application of [14C]Acetic Acid can be found in: migration in paddy soil-to-rice plant system after breakdown by microorganisms below the plow layer in geological disposal research, effects of cerulenin on the endogenous fatty acid synthetic activity in oral squamous cell carcinoma (OSCC), in vivo incorporation into goldfish liver lipids during ?-hexachlorocyclohexane exposure in aquatic toxicology, etc. ...
Proderma.ro, proderma Lapte Praf Nan 3 Comfortis x 800gr|O combinatie unica de ingrediente ce raspunde nevoilor nutritionale speciale pentru dezvoltarea normala a copilului tau.
1OX0: The 1.3-Angstrom-Resolution Crystal Structure of beta-Ketoacyl-Acyl Carrier Protein Synthase II from Streptococcus pneumoniae.
Fatty Acid Synthesis Inhibitors- Pipeline Insights, 2015, provides the in-depth analysis of the pipeline assets across the Fatty Acid Synthesis Inhibitors. The main objective of this report to track competitor pipeline molecules, related research activities, technology, collaborations, in-licensing and out-licensing deals.
TY - JOUR. T1 - Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemical conditions of the mitochondrial matrix. AU - Wagner, Gregory R.. AU - Payne, R. Mark. PY - 2013/10/4. Y1 - 2013/10/4. N2 - Background:The mechanisms initiating protein acylation in mitochondria are unknown. Results:The pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause protein lysine acetylation and succinylation. Conclusion:Protein acylation in mitochondria may be a nonenzymatic event facilitated by the alkaline pH and high acyl-CoA concentrations. Significance:The mitochondrial deacylases SIRT3 and SIRT5 may have evolved to regulate nonenzymatic protein acylation.. AB - Background:The mechanisms initiating protein acylation in mitochondria are unknown. Results:The pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause protein lysine acetylation and succinylation. Conclusion:Protein acylation in mitochondria may be a ...
Protein acylation is the post-translational modification of proteins via the attachment of functional groups through acyl linkages. Protein acylation has been observed as a mechanism controlling biological signaling.[2] One prominent type is fatty acylation, the addition of fatty acids to particular amino acids (e.g. myristoylation, palmitoylation or palmitoleoylation).[3] Different types of fatty acids engage in global protein acylation.[4] Palmitoleoylation is an acylation type where the monounsaturated fatty acid palmitoleic acid is covalently attached to serine or threonine residues of proteins.[5][6] Palmitoleoylation appears to play a significant role in trafficking and targeting and function of Wnt proteins.[7][8]. ...
TABLE-US-00001 TABLE 1 Compound Chemical Name/Structure Compound Class Abscisic acid (2Z,4E)-5-[(1S)-1-hydroxy-2,6,6-trimethyl-4- Plant Growth oxocyclohex-2-en-1-yl]-3-methylpenta-2,4-dienoic acid Hormone BPDQ 4-[(3-bromophenyl)amino]-6,7-diamino-quinazoline Kinase Inhibitor Arctigenin (3R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-3-[(4- Plant Lignan, hydroxy-3-methoxyphenyl)methyl]-2-tetrahydrofuranone Antiviral, Antitumor Baicalein 5,6,7-Trihydroxy-2-phenyl-chromen-4-one Lipoxygenase Inhibitor CDC25 Phosphatase 6-Chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline- Phosphatase Inhibitor Inhibiror I 5,8-dione Cerulenin (2R,3S)-3-[(4E,7E)-Nona-4,7-dienoyl]oxirane-2- Antifungal, Fatty carboxamide Acid Synthesis Inhibitor Eicosapentaenoic (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentenoic acid Cyclooxygenase acid Inhibitor Ethyl 4-[(hydroxyamino)-ethylamino]cyclohexa- Phosphatase Inhibitor 3,4-dephostatin 3,5-diene-1,2-dione Forskolin (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10,10b- MAP Kinase ...
3TZK: Dissecting the Structural Elements for the Activation of beta-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae.
Background Lipid oxidation of membrane phospholipids is accompanied by the formation of oxidation-specific epitopes (OSE). antibodies as a result of Siglec-G deficiency inhibits diet-induced hepatic inflammation and atherosclerosis in mice [9]. However, the relationship between plasma antibody levels targeting OSE and hepatic inflammation during NAFLD has not been investigated Lurasidone in humans so far. Here, we aimed to determine an association between plasma antibodies targeting OSE and NAFLD in humans. For this purpose, IgM and IgG antibody titers against different model epitopes of oxidized lipids were measured in the plasma of patients with NAFLD and compared to those in control subjects. Liver biopsies from patients with biopsy-proven NASH were examined for the presence of MDA epitopes by immunohistochemistry. Additionally, to test the specificity of our findings for NAFLD, antibody levels were determined in two cohorts consisting of patients with hepatitis C and inflammatory bowel ...
We describe novel imaging protocols that allow detection of small cancer cell colonies deep inside tissue phantoms with high sensitivity and specificity. to deeper tumors. We show that under these conditions Syryl-9M can detect as few as 10 cells in a biologically relevant phantom. This outstanding characteristic should bode very well for development of new highly efficient near-IR clinical imaging agents. 2. Methods 2.1. Cells and cell culture For our collagen gel phantom experiments, we required cell lines that we knew from experience would not be adversely affected by culturing in three dimensional collagen type I gels. This was true of all the cell lines used in this work. Three of the lines, normal mammary, +SA and 4T1, were also derived from the same BALB/c inbred mouse strain. The MDA-MB-231 and NIHOVCAR3 cells were chosen to represent malignant human cell lines. Passage Ambrisentan two, normal mouse mammary epithelial cells were propagated from cells obtained from Dr. H. L. Hosick in ...
R. Wagner, G. Stübiger, D. Veigel, M. Wuczkowski, P. Lanzerstorfer, J. Weghuber, E. Karteris, K. Nowikovsky, N. Wilfinger, C. Singer, R. Colomer, B. Benhamu, M. Lopez-Rodrguez, P. Valent, T. Grunt - Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells - Oncotarget, Vol. 8, No. 7, ...
Numerous medicinal plants have been reported to prevent various chronic diseases. In this study, we screened a new FASN inhibitor-alcohol extract of clove (AEC) using a fast microplate method developed in our laboratory. The major components of AEC were: eugenol (42.27%), acetyl eugenol (29.12%), ca …
Author Summary Vaccinia virus, the prototypic poxvirus, is closely related to variola virus, the etiological agent of smallpox. A full understanding of the poxviral life cycle is imperative for the development of novel antiviral therapies, the design of new vaccines, and the effective and safe use of these viruses as oncolytic agents. Metabolomic studies have shed light on the novel mechanisms used by viruses to replicate efficiently within their hosts. de novo fatty acid biosynthesis has been shown to be of relevance for numerous viral infections as well as for the development of cancer. Here we describe an important role for de novo fatty acid biosynthesis during vaccinia infection. Ongoing synthesis of palmitate is needed to fuel the production of energy within mitochondria. The biochemical events of viral DNA replication and protein synthesis are minimally affected by inhibition of this pathway, but viral assembly is disrupted more dramatically. Further exploration of this pathway will provide
Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect
The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. The product of the FAE1 gene is presumed to be a condensing enzyme that extends the chain length of fatty acids from C18 to C20 and C22. We report here the cloning of FAE1 by directed transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4. Cosegregation and reversion analyses established that the new mutant was tagged by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction and used to isolate FAE1 genomic clones and a cDNA clone from a library made from immature siliques. The predicted amino acid sequence of the FAE1 protein shares homology with those of other condensing enzymes (chalcone synthase, stilbene synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the notion that FAE1 is the structural gene for a synthase or ...
Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with four transmembrane-spanning domains that belongs to the PRAF protein family. Neuroblastoma (NB) is the most common malignant extracranial solid tumor of childhood that originates in primitive cells of the developing sympathetic nervous system. We investigated the correlation of PRAF2 mRNA expression to NB clinical and genetic parameters using Affymetrix expression analysis of a series of 88 NB tumors and examined the functional role of PRAF2 in an NB cell line using RNA interference. We found that high PRAF2 expression is significantly correlated to several unfavorable NB characteristics: MYCN amplification, high age at diagnosis, poor outcome and high INSS stage. The shRNA-mediated PRAF2 downregulation in the SK-N-SH NB cell line resulted in decreased cellular proliferation, migration and matrix-attachment. These findings were confirmed in NB patient tumor samples, where high PRAF2 expression is ...
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The function of fatty acid biosynthesis in mitochondria has remained an enigma. In eukaryotic plants, synthesis of fatty acids occurs primarily in plastids such as chloroplasts, and products of this pathway supply acyl precursors for mitochondrial and other extraplastidial membranes. The discovery of ACP in plant mitochondria (4, 5) has raised the possibility that these organelles also participate in de novo fatty acid synthesis. However, ACP has been considered to have several other functions in metabolism, and, in mitochondria, ACP is reported to be one component of the respiratory electron transport chain (14). Thus, whether ACP participates in fatty acid synthesis in plant mitochondria and what function this pathway might have in any eukaryotic organism has been unclear. In this study, we have demonstrated that the de novo synthesis of fatty acids does occur in pea mitochondria, indicating that these organelles possess the complete set of enzymes needed to assemble fatty acids. The analysis ...
Members of the Prenylated Rab acceptor domain family (PRAF) are essential for the regulation of many cellular processes [22, 23]. Here we have demonstrated that PRAF3 could induce apoptosis and inhibit migration and invasion of ESCC cells and hence may serve as a tumor suppressor in ESCC.. Although the role of PRAF3 has been studied in several other tumors using tumor cell lines [7, 9, 10, 24], there is a lack of investigation into the relationship between PRAF3 expression and the clinical features of ESCCs. In the present study, we found that the expression level of PRAF3 mRNA and protein in ESCC tissues was significantly lower than that in the matched normal tissues. In addition, we found that down-regulation of PRAF3 expression was significantly correlated with poorly differentiated grading, advanced tumor stage and lymph node metastasis of ESCC. These results would imply that PRAF3 may play an important role in regulating the progression and metastasis of ESCCs, although further in vivo ...
LB-237 Many human cancers including breast cancer exhibit increased de novo fatty acid synthesis with overexpression of fatty acid synthase (FAS). Unlike normal cells and tissues that preferentially utilize circulating fatty acids derived from the diet, cancers synthesize fatty acids endogenously for membrane biosynthesis to sustain cell proliferation. The transcription factor Sp1 is highly expressed in a variety of cancers. Sp1 regulates gene expression by interacting with GC-rich promoter sequences. Genes that regulate cell cycle progression often contain such promoter sequences, and Sp1 is critical for their expression. The promoter region of FAS also has Sp1 binding sites, and Sp1 together with sterol regulatory element-binding protein-1 (SREBP-1) has been shown to regulate FAS expression in hepatocytes. Here, we hypothesize that Sp1 coordinately regulates FAS and cell cycle progression in estrogen-responsive MCF-7 breast cancer cells. Based on previous studies, to up-regulate Sp1 activity ...
There are three groups of fatty acids, so what makes the de novo group so important? The data from Quebec clearly demonstrates that herds with more de novo fatty acids also have higher fat and protein levels in their milk. This relationship has also been demonstrated elsewhere in the world.
Definition of D-aminolevulinic acid synthase with photos and pictures, translations, sample usage, and additional links for more information.
An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O[subscript 2] concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells ...
Protein acylation is critical for many cellular functions across all domains of life. In bacteria, lipoproteins have important roles in virulence and are targets for the development of antimicrobials and vaccines. Bacterial lipoproteins are secreted from the cytosol via the Sec pathway and acylated on an N-terminal cysteine residue through the action of three enzymes. In Gram-negative bacteria, the Lol pathway transports lipoproteins to the outer membrane. Here, we demonstrate that the Aat secretion system is a composite system sharing similarity with elements of a type I secretion systems and the Lol pathway. During secretion, the AatD subunit acylates the substrate CexE on a highly conserved N-terminal glycine residue. Mutations disrupting glycine acylation interfere with membrane incorporation and trafficking. Our data reveal CexE as the first member of a new class of glycine-acylated lipoprotein, while Aat represents a new secretion system that displays the substrate lipoprotein on the cell ...
Fatty acid synthesis occurs similarly to Beta-oxidation - acetyl groups are added to a growing chain. This notes explains the fatty acid synthesis process..
Detergent ecologic praf pt. masina de spalat vase, Sonett, 3kg Varianta vrac economica Un detergent bio sub forma de pudra destinat spalarii automate a vaselor in masina de spalat vase. Chiar daca nu...
Diz eklemine ait yumuşak doku travması ve effüzyon ile başvuran hastalarda maksimal istemli izometrik egzersiz, elektrik sel kas uyarılması ve her 2 sinin birlikte uygulanmasının kuadriseps femoris kası güçlenmesi üzerine olan etkilerini ve birbirlerine karşı üstünlüklerini araştırmak amacı ile bu çalışmayı planladık. Uludağ üniversitesi Tıp Fakültesi Fiziksel Tıp ve Rehabilitasyon Kliniği-Polikliniğine başvuran 16 olgu klinik muayene, laboratuar incelemesi ve radyolojik görünümlerine dayanarak diz ekleminde akut yumuşak doku travması tanısı ile tedaviye alındı. Kuadriseps femoris kasına olguların 5 inde elektriksel kas uyarılması, 5 inde elektriksel kas uyarılması ile birlikte maksimal istemli izometrik egzersiz, 6 sında maksimal istemli isometrik egzersiz programı uygulandı.Tüm hastalar klinik olarak kuadriseps femoris kası maksimal istemli izometrik kontraksiyon gücü, 10 maksimum ağırlık kaldırma kapasitesi, uyluk ortası çevre ...
Study Flashcards On BioChem: Lipid Biosynthesis at Cram.com. Quickly memorize the terms, phrases and much more. Cram.com makes it easy to get the grade you want!
Premiul va rasplati descrierea care ma va convinge si pe mine ca imi cunosti blogul. Atentie nu trebuie nici sa ma lauzi, nici sa ma faci praf, eu nu sunt fana a extremelor, adica daca imi citesti blogul te-ai cam lamurit despre ce scriu si cum scriu. Imi doresc sa imi spui simplu si in termeni normali ce reprezinta blogul meu pentru tine si cum i-ai spune tu rapid cuiva ceva despre blogul meu. Lasa-mi textul acesta in comentariu la acest articol. ...
17. Ulusal Çocuk Cerrahisi Hemşireliği Kongresi 30 Ekim - 2 Kasım October - 2 November 2013 Eskişehir Ulusal Çocuk Cerrahisi Hemşireliği Kongresi Kurulları KONGRE ONURSAL ÜYELERİ Prof.
Lietuviu Kanadoje grupe. Naujai prisijunge nepamirskite prisistatyti kas jus sieja su Kanada, kuo uzsiimate, kokios temos domina.
Lietuviu Kanadoje grupe. Naujai prisijunge nepamirskite prisistatyti kas jus sieja su Kanada, kuo uzsiimate, kokios temos domina.
Lipid metabolism of corn (Zea mays) tissue culture was studied using seven strains or inbred lines. The lipid content from the embryogenic callus derived from these lines followed the same trend as the lipid content found in the seeds, however there was no consistent lipid pattern observed for the leaf or root callus from these same lines relative to the tissue that it originated from. Therefore corn embryogenic callus provides an ideal tissue to study lipid metabolism. Embryogenic calli were also used to select cell lines resistant to cerulenin, an inhibitor of fatty acid synthesis. While it was hypothesized that the cerulenin-resistant calli might be an overproducing-oil line, the selected resistant calli did not exhibit an increase in lipid content relative to the control calli ...
Oroxylin A Suppresses the Development and Growth of Colorectal Cancer through Reprogram of HIF1α-Modulated Fatty Acid Metabolism Researchers investigated the metabolism-modulating effects of oroxylin A on the fatty acid metabolism in colon cancer cells under hypoxia. They found that HIF1α upregulated adipophilin, fatty acid synthase and sterol regulatory element-binding protein 1, and downregulated carnitine palmitoyltransferase 1, resulting in the promoted lipid uptake and transport, increased de novo fatty acid synthesis and suppressed fatty acid oxidation. [Cell Death Dis] Full Article Aldose Reductase Inhibitor Increases Doxorubicin-Sensitivity of Colon Cancer Cells and Decreases Cardiotoxicity Scientists showed that treatment of colorectal cancer cells with fidarestat increases the efficacy of doxorubicin (DOX)-induced death in HT-29 and SW480 cells and in nude mice xenografts. Aldose reductase inhibition resulted in higher intracellular accumulation of DOX and decreased the expression of ...
We describe a new type of collective behavior in C. elegans nematodes, aggregation of starved L1 larvae. Shortly after hatching in the absence of food, L1 larvae arrest their development and disperse in search for food. In contrast, after two or more days without food, the worms change their behavior-they start to aggregate. The aggregation requires a small amount of ethanol or acetate in the environment. In the case of ethanol, it has to be metabolized, which requires functional alcohol dehydrogenase sodh-1. The resulting acetate is used in de novo fatty acid synthesis, and some of the newly made fatty acids are then derivatized to glycerophosphoethanolamides and released into the surrounding medium. We examined several other Caenorhabditis species and found an apparent correlation between propensity of starved L1s to aggregate and density dependence of their survival in starvation. Aggregation locally concentrates worms and may help the larvae to survive long starvation. This work demonstrates how
Citrate, a substance being related to de novo fatty acid synthesis and tricarboxylic acid (TCA) cycle, has a pivotal role in cell survival. However, the molecular mechanisms that regulate intracellular citrate in triple-negative breast cancer (TNBC), especially under hypoxic condition, remain poorly understood. Here we find that hypoxia (1% O2) induces DNA damage-independent ATM activation (oxidized ATM) and suppression of oxidized ATM reduces intracellular citrate via decreasing the levels of phosphofructokinase (PFKP) and citrate synthase (CS), two key glucose metabolism-associated enzymes. Mechanistically, PFKP is regulated by HIF1A at the translational level, whereas CS is of posttranscriptional regulation by UBR5-mediated ubiquitination. Interestingly, accumulation of citrate in cytoplasm or exogenous citrate significantly enhances cell migration, invasion, and metastasis of hypoxic TNBC cells in vitro and in mice xenografts. The underlying mechanism mainly involves citrate-stimulated activation of
View Notes - 44106a_Q8 from BICH 441 at Texas A&M. reactants and products and the name of the enzyme. 3. (6 pts). A and B represent intermediates in fatty acid synthesis catalyzed by fatty acid
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MetabolismFatty acid and phospholipid metabolismBiosynthesisfatty acid/phospholipid synthesis protein PlsX (TIGR00182; HMM-score: 408.3) ...
Selle testiga on võimalik kodustes tingimustes kiiresti ja lihtsalt tuvastada rasedust juba selle varajases staadiumis. Tulemused 3 minutiga. Tutvu tootega
Abstract Background In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particularly involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). Results High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among ...
View Notes - Fatty Acid Synthesis copy from BIOCHEM 1 at SUNY Old Westbury. Kho Kashfi, PhD, MSc, LRSC Fatty Acid Synthesis QuickTime and GIF decompressor are needed to seeathis pictu QuickTime and
Gary Sulikowski and co-workers from Vanderbilt have reported in ACIEE on a fatty acid synthesis that possesses a cyclopropane. ACIEE paper
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Tendonlar kası kemiğe bağlayan lifli doku bantlarıdır. Aşil tendonu baldır kasının ya da gastroknemyusun bulunduğu yerde yer alır ve topuk kemiğine ya...
In culture it produces 0.3-0.627 micrograms of helvolic acid and 0.9-4.8 micrograms of cerulenin per milliliter of culture ... Bills GF; Platas G; Gams W (November 2004). "Conspecificity of the cerulenin and helvolic acid producing 'Cephalosporium ... a common industrial fungal strain used to manufacture cerulenin was known under the invalidly published designation " ...
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The ability of cerulenin to block processing was compared with other known inhibitors. Although cerulenin was effective with ... Cerulenin is a potent inhibitor of antigen processing by antigen-presenting cells.. L D Falo Jr, B Benacerraf, L Rothstein and ... The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. This antibiotic ... Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. By these criteria this drug is shown ...
Cerulenin also reduced glioma cell clonogenic survival; incubating NSB-19 cells with 3μg/mL cerulenin reduced clonogenic cell ... Cerulenin-mediated inhibition of lipid synthesis was determined using 14C labeled acetic acid. After labeling, total lipids ... Cell cycle analysis, using flow cytometry, demonstrated that 3 μg/mL of cerulenin resulted in S-phase cell arrest 24h after ... Endogenous fatty acid synthesis in cerulenin-treated glioma cells decreased by 49%, 49.7% and 51.1% at 2 hours in NSB-19, U251 ...
... effects of cerulenin on the endogenous fatty acid synthetic activity in oral squamous cell carcinoma (OSCC), in vivo ...
... effects of cerulenin on the endogenous fatty acid synthetic activity in oral squamous cell carcinoma (OSCC), in vivo ...
Here we report that cerulenin is an effective inducer of apoptosis in different wild-type p53 and mutant p53 tumor cell lines, ... Cerulenin, a fungal metabolite, is known to be a specific inhibitor of fatty acid synthase. ... Cerulenin, a fungal metabolite, is known to be a specific inhibitor of fatty acid synthase. Here we report that cerulenin is an ... Key role of mitochondria in cerulenin-mediated apoptosis Cell Death Differ. 2002 Sep;9(9):1017-25. doi: 10.1038/sj.cdd.4401055 ...
Buy Cerulenin (synthetic) (CAS 17397-89-6), an antibiotic fatty acid synthase (FAS) inhibitor, from Santa Cruz. Purity ≥98%, MF ... Cerulenin (synthetic) (CAS 17397-89-6) Cerulenin (synthetic) , CAS 17397-89-6 is rated 5.0 out of 5 by 1. ... Cerulenin (synthetic) Product Citations See how others have used Cerulenin (synthetic). Click on the entry to view the PubMed ... Leptin and Cerulenin have both been reported to affect the rate of metabolism in mice independent of the melanocortin system, ...
Commun. 48, 649 (1972). Total synthesis of (±)-cerulenin: R. K. Boeckman, Jr., E.W. Thomas, J. Am. Chem. Soc. 99, 2805 (1977); ... cerulenin: H. Ohrui, S. Emoto, Tetrahedron Lett. 1978, 2095; J.-R. Pougny, P. Sinay, ibid. 3301. Stereoselective synthesis of ...
Cerulenin, the best known natural inhibitor of fatty acid synthase (FAS), is an epoxide produced by the fungus Cephalosporium ... 60 mg/kg/day Cerulenin for 2 days; G: 30 mg/kg/day Cerulenin for 2 days; H: vehicle, daily for 2 days; I: control. All animals ... Cerulenin Cat. No.: HY-A0210 Purity: ,99.0% Data Sheet SDS Handling Instructions ... Cerulenin treatment of ob/ob mice has obvious effects on body weight. With 2 days of treatment, body weight in treated mice is ...
Rights & permissionsfor article Key role of mitochondria in cerulenin-mediated apoptosis . Opens in a new window. ... Key role of mitochondria in cerulenin-mediated apoptosis * [email protected] ...
Identification of the active site was accomplished by tagging with 3H-cerulenin and radio sequencing of the region. Comparison ... beta-Ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin ... Identification of the active site was accomplished by tagging with 3H-cerulenin and radio sequencing of the region. Comparison ... nucleotide sequence of the fabB gene and identification of the cerulenin binding residue.}, author={Sakari Kauppinen and Mads ...
Thermo Scientific Pierce Protein A/G Plus Agarose is an exceptionally high-capacity Protein A/G beaded agarose resin for use in a variety of antibody affinity purification methods ...
IMPLICATIONS FROM THE CRYSTAL STRUCTURE OF A COMPLEX WITH THE INHIBITOR CERULENIN. ... Cerulenin is covalently attached to the active site cysteine through its C2 carbon atom. The fit of the inhibitor to the active ... The crystal structure of the complex of the enzyme from Escherichia coli, and the fungal mycotoxin cerulenin reveals that the ... Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.. Moche, ...
... produce significantly less TSST-1 in the presence of cerulenin. At the concentrations tested, cerulenin reduced the amount of ... aureus in the presence of cerulenin. The effect of the test compounds was determined by placing the desired concentration, ... aureus in the presence of cerulenin. The effect of the test compound was determined by placing the desired concentration, ... produced significantly less TSST-1 in the presence of cerulenin. At the concentration tested, these compounds reduced the ...
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One of the most widely used inhibitors of FASN, cerulenin, is a natural product of Cephalosporium caerulens. Cerulenin is ... Cerulenin Topoisomerase I SN-38 Fatty acid synthase PUFA. Issue Date. 2013. Publisher. APOPTOSIS. Series/Report no.. APOPTOSIS ... These results will help determine the molecular basis of the cerulenin and SN-38 drug combination. Further investigation of ... Fatty acid synthase inhibitor cerulenin inhibits topoisomerase I catalytic activity and augments SN-38-induced apoptosis. ...
In culture it produces 0.3-0.627 micrograms of helvolic acid and 0.9-4.8 micrograms of cerulenin per milliliter of culture ... Bills GF; Platas G; Gams W (November 2004). "Conspecificity of the cerulenin and helvolic acid producing Cephalosporium ... a common industrial fungal strain used to manufacture cerulenin was known under the invalidly published designation " ...
Crystal Structure of Cerulenin Bound Xanthomonas Campestri Olea (Co- Crystal) Xe Derivative ... The binding sites of Manganese atom in the structure of Crystal Structure of Cerulenin Bound Xanthomonas Campestri Olea (Co- ... Manganese in the structure of Crystal Structure of Cerulenin Bound Xanthomonas Campestri Olea (Co- Crystal) Xe Derivative (pdb ...
Treatment with cerulenin or a novel small-molecule inhibitor of FAS C75 resulted in a dramatic accumulation of CDKi p27KIP1, ... In SK-Br3 cells, cerulenin-induced inhibition of FAS activity resulted in down-regulation of p53, and up-regulation of cyclin- ... Pharmacological inhibition of FAS activity by the natural antibiotic cerulenin [(2S,3R)-2,3-epoxy-4-oxo-7E,10E-dodecadienamide ... were unable to rescue breast cancer cells from cerulenin-induced cytotoxicity. Pharmacological blockade of FAS activity in FAS- ...
Boekman, R.K., and Thomas, E.W. (1979). A total synthesis of dl-cerulenin. J. Am. Chem. Soc. 101, 987-994.CrossRefGoogle ... Omura, S. (1976). The antibiotic cerulenin, a novel tool for biochemistry as in inhibitor of fatty acid synthesis. Bacteriol. ... Inhibition of fatty acid synthetase by the antibiotic cerulenin. Biochem. Biophvs. Res. Commun., 48, 649-656.CrossRefGoogle ...
Cerulenin. Approved. *MalaCards. *Medline Plus. Pharma. Target, inhibitor. 0. Isoniazid. Approved. *MalaCards ...
Cerulenin. 15 min. ↓ UPC2, ↑ ATP. Platinum nanoparticles. ↓ Hepatic injury. Exendin 4. 20 min. ↓ Hepatic injury and autophagy. ...
Cells were then washed and diluted in liquid YPD medium containing either 10 μg of cerulenin (ICN Biomedicals, Irvine, Calif.) ... but this time neutral lipid mobilization was induced by inhibiting de novo fatty acid synthesis with cerulenin (38). Under ... mobilization was analyzed after dilution of the cells in medium containing cerulenin. Lipids were extracted and analyzed by TLC ...
Cerulenin. The risk or severity of adverse effects can be increased when Cerulenin is combined with Perhexiline.. Approved. ...
1994 Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene. Mol. Gen. Genet. 244: 90 ... 1991); cerulenin, inhibits fatty acid synthesis (Inokoshiet al. 1994); clotrimazole, inhibits ergosterol synthesis (Sud and F ...
A few years ago on this blog, I wrote several times about a small company called Zafgen and their unusual epoxide-based chemical matter (beloranib) that was in
A. Matsumae, S. Nomura, and T. Hata, "Studies on cerulenin. IV. Biological characteristics of cerulenin," The Journal of ... Previously two classes of inhibitor, cerulenin [5] and thiolactomycin [6-8], were reported, but inhibitory activity was poor ( ... cerulenin is a powerful inhibitor of polyketide synthesis). An organism producing a fatty acid synthesis inhibitor must retain ...
HPLC Application #20027: Multi-Class Screening of 243 Mycotoxins by LC/MS/MS. Column used: Gemini® 5 µm C18 110 Å, LC Column 150 x 4.6 mm, Ea Part#: 00F-4435-E0
cerulenin CHLORMETHIAZOLE chlorogenic acid chlorprothixene chrysophanol CINANSERIN cirazoline cisapride CITCO clofenotane ...
This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on ... It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal ...
Cerulenin from Cephalosporium Caerulens *Cerulex - Pfizer *Cerulisina - Bouty *Ceruloplasmin - Microgen NPO; Immunopreparat * ...
Subinhibitory cerulenin inhibits staphylococcal exoprotein production by blocking transcription rather than by blocking ...
B, cerulenin, c75, and TOFA inhibit fatty acid synthesis to 60% or less of control levels at the doses used (μg/ml). C and E, ... 1) ⇓ . When proliferating cells were exposed to 10 μg/ml cerulenin, there was a redistribution of cells into S phase and G2-M ... 13 and 19 and data not shown). Entry into apoptosis after FAS inhibition by cerulenin occurred from G1, S, and G2-M without ... Cerulenin, (2R, 3S)-2,3-epoxy-4-oxo-7,10-trans, transdodecadienamide, a natural product of Cephalosporium caerulens, is a ...
  • Here we report that cerulenin is an effective inducer of apoptosis in different wild-type p53 and mutant p53 tumor cell lines, whereas normal human keratinocytes and fibroblasts are resistant to the apoptotic effect. (nih.gov)
  • To get more insight into the mechanisms of how cerulenin induces apoptosis we investigated several signal transduction molecules, including p53, p73, p21/WAF1, Bax, cytochrome c, and caspases 3 and 9. (nih.gov)
  • The significance of the mitochondrial pathway for the cerulenin-mediated apoptosis was confirmed by the rapid mitochondrial release of cytochrome c both in wild-type p53 and mutant cell lines. (nih.gov)
  • Mitochondrial investigations indicate that cerulenin induces apoptosis in a caspase-dependent manner in A-375 cells. (scbt.com)
  • In most cell lines showing overexpression of FASN, the FASN inhibitor Cerulenin markedly decreased FASN expression, cell viability, and induced apoptosis. (scbt.com)
  • Because of the widespread clinical interest in combining cerulenin with other chemotherapeutic agents, we performed this study to gain insight into the downstream effects of FASN inhibition that lead to apoptosis. (inha.ac.kr)
  • We identified topoisomerase I as a potential mediator of cerulenin-induced apoptosis, possibly by upregulating intracellular polyunsaturation. (inha.ac.kr)
  • Our results suggest that topoisomerase I could participate in cerulenin-induced apoptosis by upregulating intracellular polyunsaturation. (inha.ac.kr)
  • moreover, the pan-caspase inhibitor Z-VAD-FMK did not inhibit Cerulenin-induced apoptosis and cell death. (harvard.edu)
  • In addition, treatment of MM cells with Cerulenin primarily up-regulated apoptosis-inducing factor/endonuclease G, mediators of caspase-independent apoptosis. (harvard.edu)
  • Although the C-Jun-NH2-terminal kinase (JNK) inhibitor SP600215 blocked Cerulenin-induced cytotoxicity, it did not inhibit apoptosis and caspase cleavage. (harvard.edu)
  • Our results therefore indicate that inhibition of FAS by Cerulenin primarily triggered caspase-independent apoptosis and JNK-dependent cytotoxicity in MM cells. (harvard.edu)
  • Furthermore, inhibition of FAS activity by cerulenin or C75 resulted in downregulation of phospho-AKT, which preceded the induction of apoptosis. (elsevier.com)
  • Cerulenin is an antibiotic and antifungal agent originally isolated from Cephalosporium caerulens . (scbt.com)
  • Cerulenin, the best known natural inhibitor of fatty acid synthase ( FAS ), is an epoxide produced by the fungus Cephalosporium caeruleus . (medchemexpress.com)
  • For forty years prior to 2005, a common industrial fungal strain used to manufacture cerulenin was known under the invalidly published designation "Cephalosporium caerulens", but an isolate of the original C. caerulens strain KF-140 was subsequently shown to be conspecific with S. oryzae. (wikipedia.org)
  • Treatment with cerulenin or a novel small-molecule inhibitor of FAS C75 resulted in a dramatic accumulation of CDKi p27KIP1, which was accompanied by a noteworthy translocation of p27KIP1 from cytosol to cell nuclei. (nih.gov)
  • This study investigated the biological significance of the inhibition of fatty acid synthase (FAS) in multiple myeloma (MM) using the small molecule inhibitor Cerulenin. (harvard.edu)
  • This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. (rcsb.org)
  • The experiments showed that the MexAB-OprM system is responsible for the intrinsic resistance of this bacterium to cerulenin and thiolactomycin. (asm.org)
  • Whereas thiolactomycin was not a substrate of the MexCD-OprJ pump expressed in a Δ( mexAB-oprM ) nfxB mutant, cerulenin was efficiently effluxed by the MexCD-OprJ system. (asm.org)
  • Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. (pdbj.org)
  • Pharmacological inhibition of FAS activity by the natural antibiotic cerulenin [(2S,3R)-2,3-epoxy-4-oxo-7E,10E-dodecadienamide] resulted in a dose-dependent cytotoxicity which positively paralleled the endogenous level of FAS. (nih.gov)
  • In SK-Br3 cells, cerulenin-induced inhibition of FAS activity resulted in down-regulation of p53, and up-regulation of cyclin-dependent kinase inhibitor (CDKi) p21WAF1/CIP1. (nih.gov)
  • C75, a synthetic analogue of cerulenin, is also a potent FASN inhibitor ( 11 ), which is cytotoxic for various tumor cell lines in vitro ( 12 , 13 ), and shows significant in vivo antitumor activity against human cancer cell xenografts ( 14 , 15 ). (aacrjournals.org)
  • We demonstrate that pharmacologic manipulation of FASN or SCD1 enzymatic activity by non-toxic concentrations of cerulenin or CAY10566 decreases CHIKV genome replication. (medworm.com)
  • Cerulenin was used as a FASN inhibitor. (readbyqxmd.com)
  • Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. (jimmunol.org)
  • Leptin and Cerulenin have both been reported to affect the rate of metabolism in mice independent of the melanocortin system, with the difference being that cerulenin does not inhibit the neuroendocrine effects of fasting in mice. (scbt.com)
  • The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. (jimmunol.org)
  • Taken together, these results suggest that the effect of cerulenin may define a distinct step in antigen processing and provides evidence that some other processing events are not universally required. (jimmunol.org)
  • Here, we observed the increased antitumor effect of cerulenin when combined with the topoisomerase inhibitor SN-38. (inha.ac.kr)
  • The labeling of pea H protein was inhibited by addition of cerulenin into the assay medium. (pnas.org)
  • They were able to isolate the two bottlenecks in the procedures and from there optimized the pathway with the addition of cerulenin (an antibiotic) leading to the production of 70mg/L of pinoslyvin from glucose. (prezi.com)
  • Cerulenin, a fungal metabolite, is known to be a specific inhibitor of fatty acid synthase. (nih.gov)
  • To explore the underlying mechanism of Steroidogenic acute regulatory protein (StAR)'s protective effect on endothelial dysfunction model, the inhibitor of fatty acid synthase and HMG-CoA reductase, Cerulenin ( 5 μg/mL) and Lovastatin, are used before palmitic acid (PA) added. (medchemexpress.com)
  • Embryogenic calli were also used to select cell lines resistant to cerulenin, an inhibitor of fatty acid synthesis. (illinois.edu)
  • The crystal structure of the complex of the enzyme from Escherichia coli, and the fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic pocket formed at the dimer interface. (rcsb.org)
  • Clarification of fatty acid synthase and the reaction mechanism of an antibiotic, cerulenin (Kawaguchi). (nii.ac.jp)
  • First, we analysed the effect of the antibiotic cerulenin, showing that DHA production increased twofold. (biomedcentral.com)
  • However, the overexpression of this mutant did not affect the anorectic actions of leptin or central cerulenin for which an increase in Arc malonyl-CoA level is also required. (physiology.org)
  • omega-3 (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) and omega-6 (linoleic acid and arachidonic acid) polyunsaturated fatty acids (PUFAs), however, were unable to rescue breast cancer cells from cerulenin-induced cytotoxicity. (nih.gov)
  • and (3) cerulenin mediated cytotoxicity is due in part to apoptotic cell death and cell cycle arrest. (aacrjournals.org)
  • MCF-7 cells became insensitive to C75-induced cytotoxicity when the expression of FAS was specifically suppressed by targeted knock-down with small interfering RNA (siRNA), whereas they partially retained their sensitivity to cerulenin. (ingentaconnect.com)
  • Cerulenin is selectively toxic to human cancer cells in vitro. (inha.ac.kr)
  • This increased sensitivity is readily demonstrated in vivo, but in vitro we failed to detect an increased sensitivity of the Vtr synthase II to cerulenin, nor have we detected any other kinetic or structural alteration in the enzyme. (asm.org)
  • Resistance to cerulenin in S. cerevisiae was mapped to FAS2 , and inhibition of the encoded enzyme, fatty acid synthase, was demonstrated biochemically ( 21 ). (asm.org)
  • Finally, we show that suppressing topoisomerase I catalytic activity results in synergistic effects between cerulenin and LY294002. (inha.ac.kr)
  • Furthermore, Cerulenin showed synergistic cytotoxic effects with various agents including Bortezomib, Melphalan and Doxorubicin. (harvard.edu)
  • While it was hypothesized that the cerulenin-resistant calli might be an overproducing-oil line, the selected resistant calli did not exhibit an increase in lipid content relative to the control calli. (illinois.edu)
  • the number of G0/G1 and G2/M cells was decreased Further, treatment with cerulenin resulted in dose- and time-dependent decreases in glioma cell viability, assessed using the MTT assay. (aacrjournals.org)
  • Cerulenin covalently binds to the catalytic site of FAS and disrupts the condensation reaction of acetyl-COA and malonyl-COA, inhibiting the biosynthesis of fatty acids and sterols in yeast. (medchemexpress.com)
  • Cerulenin is covalently attached to the active site cysteine through its C2 carbon atom. (rcsb.org)
  • Our data strongly indicate that mitochondria play a key role in the cerulenin-mediated pathway. (nih.gov)
  • Importantly, Cerulenin induced endoplasmic reticulum stress response via up-regulation of the Grp78/IRE1\(\alpha\)/JNK pathway. (harvard.edu)
  • To obtain analogues with all structural features of cerulenin including two double bonds and the epoxide function, a third pathway was chosen. (uni-wuerzburg.de)
  • Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. (medchemexpress.com)
  • Increased apoptotic cell death and activated caspase-3 expression was observed in U251 and NSB-19 cells treated with cerulenin. (aacrjournals.org)
  • beta-Ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin binding residue. (semanticscholar.org)
  • To determine whether the up-regulation of TP53 following exposure to cerulenin or C75 was solely due to inhibition of endogenous fatty acid metabolism, we first evaluated the cytotoxic response to chemical FAS blockers on MCF-7 cells in which FAS gene expression was previously silenced by using the highly sequence-specific mechanism of RNA interference. (ingentaconnect.com)
  • The medium was changed to stalk salts, cerulenin at concentrations between 50 μM and 150 μM, and 5 mM cAMP, and was incubated for a further 6 hours. (biologists.org)
  • Cerulenin treatment of ob/ob mice has obvious effects on body weight. (medchemexpress.com)
  • Treatment with either cerulenin or C75 induced TP53 protein accumulation at 24 h in MCF-7 cells. (ingentaconnect.com)
  • To include the epoxide function especially with regard to the mechanism of action of cerulenin in the FAS system (considering known crystal structures of cerulenin and the KasA analogue of E. coli) tetrahydro- and dihydrocerulenin analogues were synthesized. (uni-wuerzburg.de)
  • The MICs of the Fluconazole and Cerulenin controls are 63 and 125 μg/mL for the wild-type strain and 30 and 15 μg/mL for the mutant strain, respectively [1] . (medchemexpress.com)
  • The combination of cerulenin inhibition and fabH deletion rendered a 6.5-fold improvement compared to control strain. (biomedcentral.com)
  • If given daily or every other day, ATP content are increased 58.1% and 61.5% respectively by 7-day treatment of 60 mg/kg Cerulenin. (medchemexpress.com)
  • Significant ATP elevation is also observed with only 2 days of treatment with 60 mg/kg Cerulenin. (medchemexpress.com)
  • Supraphysiological levels of exogenous oleic acid (OA), a omega-9 monounsaturated fatty acid synthesized from a primary-end product of FAS palmitate, significantly diminished cell toxicity caused by cerulenin. (nih.gov)
  • Cerulenin was chosen as the lead structure, being a substrate of the efflux pumps in Candida albicans on one hand and therefore variations on the structure could lead to a blocking of the efflux pumps as in the case of tetracycline and inhibitor 13-CPTC of the TetB efflux pump. (uni-wuerzburg.de)
  • The incorporation of radioactivity from [2- 14 C]malonate into fatty acids and the labeling of ACP were inhibited by cerulenin and required ATP and Mg 2+ . (pnas.org)
  • In culture it produces 0.3-0.627 micrograms of helvolic acid and 0.9-4.8 micrograms of cerulenin per milliliter of culture medium. (wikipedia.org)
  • These results will help determine the molecular basis of the cerulenin and SN-38 drug combination. (inha.ac.kr)
  • Although cerulenin was effective with all antigens tested, at least one inhibitor was not. (jimmunol.org)
  • In all groups, 60 mg/kg of Cerulenin is more effective than 30 mg/kg in inhibiting weight gain. (medchemexpress.com)