L-CYSTEINE PROMOTES THE PROLIFERATION AND DIFFERENTIATION OF NEURAL STEM CELLS VIA THE CBS/H2S PATHWAY

被引:62
作者
Wang, Z. [1 ,2 ]
Liu, D. -X. [1 ]
Wang, F. -W. [1 ]
Zhang, Q. [1 ]
Du, Z. -X. [1 ]
Zhan, J. -M. [1 ]
Yuan, Q. -H. [1 ]
Ling, E. -A. [3 ]
Hao, A. -J. [1 ]
机构
[1] Shandong Univ, Minist Educ Expt Teratol, Shandong Prov Key Lab Mental Disorders, Key Lab,Dept Histol & Embryol,Sch Med, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Inst Physiol, Sch Med, Jinan 250012, Shandong, Peoples R China
[3] Natl Univ Singapore, Dept Anat, Yong Loo Lin Sch Med, Singapore 117597, Singapore
基金
中国国家自然科学基金;
关键词
(L)-cysteine; neural stem cells; proliferation; differentiation; CYSTATHIONINE BETA-SYNTHASE; HYDROGEN-SULFIDE; NG108-15; CELLS; INVOLVEMENT; EXPRESSION; INHIBITOR; KINASE; DAMAGE;
D O I
10.1016/j.neuroscience.2012.12.057
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:106 / 117
页数:12
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