acyl-CoA Synthetase (acyl-coa + synthetase)

Distribution by Scientific Domains

Kinds of acyl-CoA Synthetase

  • fatty acyl-coa synthetase


  • Selected Abstracts


    Acyl-CoA synthetase as a cancer survival factor: its inhibition enhances the efficacy of etoposide

    CANCER SCIENCE, Issue 8 2009
    Tetsuo Mashima
    Lipid metabolism is often elevated in cancer cells and plays an important role in their growth and malignancy. Acyl-CoA synthetase (ACS), which converts long-chain fatty acids to acyl-CoA, is overexpressed in various types of cancer. However, the role of ACS in cancer remains unknown. Here, we found that ACS enzyme activity is required for cancer cell survival. Namely, the ACS inhibitor Triacsin c induced massive apoptosis in glioma cells while this cell death was completely suppressed by overexpression of ACSL5, the Triacsin c,resistant ACS isozyme, but not by overexpression of a catalytically inactive ACSL5 mutant. ACS inhibition by Triacsin c markedly potentiated the Bax-induced intrinsic apoptotic pathway by promoting cytochrome c release and subsequent caspase activation. These effects were abrogated by ACSL5 overexpression. Correspondingly, ACS inhibition synergistically potentiated the glioma cell death induced by etoposide, a well-known activator of apoptosis. Furthermore, in a nude mouse xenograft model, Triacsin c at a non-toxic dose enhanced the antitumor efficacy of a low-dose chemotherapy with etoposide. These results indicate that ACS is an apoptosis suppressor and that ACS inhibition could be a rational strategy to amplify the antitumor effect of etoposide. (Cancer Sci 2009) [source]


    Subcellular distribution of key enzymes of lipid metabolism during the euthermia-hibernation-arousal cycle

    JOURNAL OF ANATOMY, Issue 6 2009
    Anna Suozzi
    Abstract Mammalian hibernation is a natural, fully reversible hypometabolic state characterized by a drastic reduction of body temperature and metabolic activity, which ensures survival to many species under adverse environmental conditions. During hibernation, many hibernators rely for energy supply almost exclusively on lipid reserves; the shift from carbohydrate to lipid metabolism implies profound rearrangement of the anabolic and catabolic pathways of energetic substrates. However, the structural counterpart of such adaptation is not known. In this study we investigated, by using immunoelectron microscopy, the fine intracellular distribution of two key enzymes involved in lipid metabolism, namely, the fatty acid synthase (FAS) and the long-chain fatty acyl-CoA synthetase (ACSL), in hepatocytes of euthermic, hibernating and arousing hazel dormice. Our results show that the two enzymes are differentially distributed in cellular compartments (cytoplasm, mitochondria and cell nuclei) of hepatocytes during euthermia. Quantitative redistribution of both enzymes among cellular compartments takes place during hibernation and arousal, in accordance with the physiological changes. Interestingly, this redistribution follows different seasonal patterns in cytoplasm, mitochondria and nuclei. In conclusion, our data represent the first quantitative morphological evidence of lipid enzyme distribution in a true hibernator throughout the year cycle, thus providing a structural framework to biochemical changes associated with the hypometabolism of hibernation. [source]


    ,-Synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    JOURNAL OF NEUROCHEMISTRY, Issue 1 2007
    Mikhail Y. Golovko
    Abstract Previously, we demonstrated that ablation of ,-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown. In the present study, we examined the effect of Snca gene ablation on brain 22:6n-3 metabolism. We determined 22:6n-3 uptake and incorporation into brain phospholipids by infusing awake, wild-type and Snca,/, mice with [1- 14C]22:6n-3 using steady-state kinetic modeling. In addition, because Snca modulates 20:4n-6-CoA formation, we assessed microsomal Acsl activity using 22:6n-3 as a substrate. Although Snca gene ablation does not affect brain 22:6n-3 uptake, brain 22:6n-3-CoA mass was elevated 1.5-fold in the absence of Snca. This is consistent with the 1.6- to 2.2-fold increase in the incorporation rate and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 0.5 ,mol/L, it did not bind 22:6n-3-CoA. These effects of Snca gene deletion on 22:6n-3 brain metabolism are opposite to what we reported previously for brain 20:4n-6 metabolism and are likely compensatory for the decreased 20:4n-6 metabolism in brains of Snca,/, mice. [source]


    Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2008
    Wei Ji
    ABSTRACT In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid ,-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7,-hydroxylase contributed to cholesterol metabolism, leading to decreases in serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism were systemically modulated by CM108, which contributed to the improvement of lipid profiles in hyperlipidaemic rats. [source]


    Characterization of a Cryptosporidium parvum Gene Encoding a Protein with Homology to Long Chain Fatty Acid Synthetase

    THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2003
    Leonardo Camero
    ABSTRACT: We describe here the cloning, sequencing, and characterization of a novel Cryptosporidium parvum gene, encoding a protein with significant homology to the long-chain fatty acyl-CoA synthetase (LCFA, EC 6.2.13). The gene has an open reading frame of 2,301 bp, coding for a 766 amino acid polypeptide, and with an estimated MW of 86.1 kDa. By indirect immunofluorescence assay, monoclonal antibodies C3CE7 and ESD labeled the anterior pole of fixed C. parvum sporozoites and developmental stages in C. parvum-infected cultures at 24, 48, and 72 h post-infection. These monoclonal antibodies inhibited more than 3.5% of parasite growth in vitro. The effect of triacsin C, a potent selective inhibitor of LCFA synthetase, on parasite growth was assessed in cell culture; complete inhibition of parasite growth at 2.5 ug/inl was obtained with little evidence of drug-associated cytotoxicity. These results suggest that the fatty acyl-CoA synthetase may be a useful target in the development of selective inhibitors and immunologic interventions against C. parvum [source]


    Gene expression of fatty acid-binding proteins, fatty acid transport proteins (cd36 and FATP) and ,-oxidation-related genes in Atlantic salmon (Salmo salar L.) fed fish oil or vegetable oil

    AQUACULTURE NUTRITION, Issue 4 2009
    B.E. TORSTENSEN
    Abstract Relative gene expression pattern of fatty acid transport proteins (FATP and cd36), intracellular fatty acid-binding proteins (FABP3, FABP10 and FABP11), ,-oxidation-related genes [carnitine palmitoyl transferase II (CPTII), peroxisome proliferator-activated receptor , (PPAR,), acyl-CoA oxidase (AOX), long-chain fatty acyl-CoA synthetase (FACS), acyl-CoA dehydrogenase (dehydrogenase)] and uncoupling protein 2 (UCP2) was assessed by RT-qPCR in Atlantic salmon muscle (red and white), liver, heart, myosepta and visceral fat. FABP11, a FABP isoform not previously described in Atlantic salmon, was highly expressed in visceral fat and myosepta and at the lower level in red muscle, white muscle, myosepta and heart. Furthermore, Atlantic salmon were fed either a diet containing fish oil (FO) or a complete replacement of FO with a vegetable oil blend (55% rapeseed oil, 30% palm oil and 15% linseed oil; VO) for the production cycle (27 months from start of feeding and until ,4.5 kg mean weight). The expression of genes related to ,-oxidation, fatty acid uptake and transport in the white muscle indicate (n = 3) significant down-regulation in VO fed Atlantic salmon and correlated with previously reported white muscle triacylglycerol stores and ,-oxidation. FABP11 in visceral fat and myosepta was also down-regulated in VO fed fish. [source]


    Auraptene, a citrus fruit compound, regulates gene expression as a PPAR, agonist in HepG2 hepatocytes

    BIOFACTORS, Issue 1 2008
    Nobuyuki Takahashi
    Abstract Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-, (PPAR,) activation. To examine effects of auraptene on the PPAR, activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPAR, expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPAR, chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPAR,-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPAR, because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPAR,-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPAR, agonist in hepatocytes and that auraptene may improve lipid abnormality through PPAR, activation in the liver. [source]