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.
Kee
Hae Jin
HJ
Research Institute of Medical Sciences, Chonnam National University, Kwangju 501-190, South Korea.
Koh
Jeong Tae
JT
Yang
Sung Yeul
SY
Lee
Zang Hee
ZH
Baik
Yung Hong
YH
Kim
Kyung Keun
KK
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003001:Cloning, Molecular; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D016716:PC12 Cells; D051381:Rats; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014226:Triazenes / Q000494:pharmacology; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D004791:Enzyme Inhibitors; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014226:Triazenes; C034613:triacsin C; D020932:Nerve Growth Factor; D006899:Mixed Function Oxygenases; C491170:Phyh protein, mouse; C491171:Phyh protein, rat; D003066:Coenzyme A Ligases; C475689:Acsl6 protein, mouse; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase