L-CYSTEINE PROMOTES THE PROLIFERATION AND DIFFERENTIATION OF NEURAL STEM CELLS VIA THE CBS/H2S PATHWAY
L-CYSTEINE PROMOTES THE PROLIFERATION AND DIFFERENTIATION OF NEURAL STEM CELLS VIA THE CBS/H2S PATHWAY
复制标题
L-半胱氨酸通过CBS/H2S途径促进神经干细胞的增殖和分化
DOI：
10.1016/j.neuroscience.2012.12.057
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发表时间：
2013-05-01
期刊：
影响因子：
3.3
通讯作者：
Hao, A. -J.
中科院分区：
文献类型：
--
作者：
Wang, Z.;Liu, D. -X.;Hao, A. -J.
越来越多的证据表明，硫化氢(H_2S)是一种新型的神经调节剂和神经保护剂，但H_2S对神经干细胞(NSCs)是否有直接作用仍有待研究。本文报道神经干细胞表达半胱氨酸p合酶，外源性H_2S供体L半胱氨酸可刺激神经干细胞增殖，增强神经干细胞向神经元和星形胶质细胞的分化潜能。此外，预先给予CBS的抑制剂氨基氧乙酸或阻断CBS的siRNA，可显著减弱L-半胱氨酸对H_2S水平升高和细胞增殖的影响，并有效地抑制L-半胱氨酸诱导的神经发生和星形胶质细胞发生。进一步分析发现，L-半胱氨酸诱导的细胞增殖与细胞外信号调节蛋白1/2的磷酸化和分化相关基因的表达改变有关。综上所述，本研究结果提示L-半胱氨酸可通过CBS/H_2S途径促进神经干细胞的增殖和分化，这可能为阐明其在生理和病理环境中调控神经干细胞命运的作用提供有用的推测。(C)2013年IBRO。爱思唯尔有限公司出版。保留所有权利。
Growing evidence has suggested that hydrogen sulfide (H2S) acts as a novel neuro-modulator and neuroprotective agent; however, it remains to be investigated whether H2S has a direct effect on neural stem cells (NSCs). We report here that NSCs expressed cystathionine p synthase (CBS) and addition of exogenous H2S donor, L-cysteine, stimulated proliferation and increased the differentiation potential of NSCs to neurons and astroglia. Moreover, pre-treatment with aminooxyacetic acid, the inhibitor of CBS or knockdown of CBS in using siRNA, significantly attenuated the effects of L-cysteine on elevated H2S levels and the cell proliferation; it also effectively suppressed L-cysteine-induced neurogenesis and astrocytogenesis. Further analysis revealed that L-cysteine-induced proliferation was associated with phosphorylation of extracellular signal-regulated kinases 1/2 and differentiation with altered expression of differentiation-related genes. Taken together, the present data suggest that L-cysteine can enhance proliferation and differentiation of NSCs via the CBS/H2S pathway, which may serve as a useful inference for elucidating its role in regulating the fate of NSCs in physiological and pathological settings. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.