Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oleamide is an endogenous sleep-inducing lipid that has been isolated from the cerebrospinal fluid of sleep-deprived mammals. Oleamide is the best-understood member of the primary fatty acid amide family. One key unanswered question regarding oleamide and all other primary acid amides is the pathway by which these molecules are produced. One proposed pathway involves oleoyl-CoA and N-oleoylglycine as intermediates: oleic acid --> oleoyl-CoA --> N-oleoylglycine --> oleamide. The first and third reactions are known reactions, catalyzed by acyl-CoA synthetase and peptidylglycine alpha-amidating monooxygenase (PAM). Oleoyl-CoA formation from oleic acid has been demonstrated in vitro and in vivo while, to date, N-oleoylglycine cleavage to oleamide has been established only in vitro. PAM catalyzes the final step in alpha-amidated peptide biosynthesis, and its proposed role in primary fatty acid amide biosynthesis has been controversial. Mouse neuroblastoma N(18)TG(2) cells are an excellent model system for the study of oleamide biosynthesis because these cells convert [(14)C]-oleic acid to [(14)C]-oleamide and express PAM in a regulated fashion. We report herein that growth of the N(18)TG(2) cells in the presence of [(14)C]-oleic acid under conditions known to stimulate PAM expression generates an increase in [(14)C]-oleamide or in the presence of a PAM inhibitor generates [(14)C]-N-oleoylglycine. This represents the first identification of N-oleoylglycine from a biological source. In addition, N(18)TG(2) cell growth in the presence of N-oleoylglycine yields oleamide. These results strongly indicate that N-oleoylglycine is an intermediate in oleamide biosynthesis and provide further evidence that PAM does have a role in primary fatty acid amide production in vivo.
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PMID:Oleic acid derived metabolites in mouse neuroblastoma N18TG2 cells. 1544 56

Lipogenesis is crucial during neuronal development. Abnormal lipid metabolism causes neurological disorders such as Refsum disease and contributes to tumor formation. Long-chain acyl-CoA synthetase (Acsl) ligates coenzyme A to fatty acids, thereby activating the lipid metabolism pathway. Here, we designed a specific small interference RNA (siRNA) against mouse Acsl6, pU6-487i and pU6-586i, and investigated the function of Acsl6 in neuron differentiation. Expression of mAcsl6 mRNA and protein was markedly decreased by pU6-487i and pU6-586i in NB41A3 mouse neuroblastoma cells. We established two stable cell lines, NB41A3-487 and NB41A3-586, which expressed mAcsl6 siRNA. Knockdown of the mAcsl6 gene inhibited the proliferation of NB41A3 cells; in NB41A3-586 cells neurite outgrowth was suppressed, while in NB41A3-487 cells it was almost absent. In addition, pU6-487i was more effective than pU6-586i in the reduction of cell proliferation and neurite outgrowth. The decline noted in the growth curves as well as the neurite outgrowth resulting from mAcsl6 knockdown indicate that the mAcsl6 gene plays a pivotal role in neuron development.
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PMID:RNA interference of long-chain acyl-CoA synthetase 6 suppresses the neurite outgrowth of mouse neuroblastoma NB41A3 cells. 2147 84