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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