A novel murine long-chain acyl-CoA synthetase expressed in brain participates in neuronal cell proliferation.
Refsum disease (RfD) is an autosomal recessive neurologic disorder of the lipid metabolism. We have identified a novel murine long-chain acyl-CoA synthetase (mLACS) associated with the RfD gene using yeast two-hybrid assay. Northern blot analyses revealed that mLACS was expressed mainly in the brain and testis. mLACS was highly expressed ... in the brain at 2 weeks after birth and maintained through adult life. Expressions of the brain-specific LACS family increased in the PC12 cells undergoing neurite outgrowth by nerve growth factor. mLACS preferentially catalyzed the formation of arachidonoyl-CoA more than palmitoyl-CoA or oleoyl-CoA in PC12 cells. Triacsin C, an inhibitor of LACS, suppressed the cell proliferation and decreased mLACS expression in parent PC12 cells, but not in stably anti-sense mLACS cDNA-transfected cells. Our results indicate that mLACS participates in neuronal cell proliferation and differentiation, and interaction of the RfD gene with brain-selective mLACS may be involved in the pathogenesis of RfD.
Mesh Terms:
Amino Acid Sequence, Animals, Brain, Cell Division, Cell Line, Cell Survival, Cloning, Molecular, Coenzyme A Ligases, Enzyme Inhibitors, Mice, Mixed Function Oxygenases, Molecular Sequence Data, Nerve Growth Factor, Neurons, PC12 Cells, Rats, Repressor Proteins, Saccharomyces cerevisiae Proteins, Sequence Alignment, Tissue Distribution, Transcription, Genetic, Triazenes
Amino Acid Sequence, Animals, Brain, Cell Division, Cell Line, Cell Survival, Cloning, Molecular, Coenzyme A Ligases, Enzyme Inhibitors, Mice, Mixed Function Oxygenases, Molecular Sequence Data, Nerve Growth Factor, Neurons, PC12 Cells, Rats, Repressor Proteins, Saccharomyces cerevisiae Proteins, Sequence Alignment, Tissue Distribution, Transcription, Genetic, Triazenes
Biochem. Biophys. Res. Commun.
Date: Jun. 13, 2003
PubMed ID: 12767919
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