4.5 Article

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

Journal

NEUROSCIENCE
Volume 237, Issue -, Pages 106-117

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2012.12.057

Keywords

(L)-cysteine; neural stem cells; proliferation; differentiation

Categories

Funding

  1. National Natural Science Foundation of China [81071057, 81200879]
  2. Ministry of Education of China [20110131110036]
  3. Natural Science Foundation of Shandong Province [2012JC006, ZR2011HQ035, ZR2012HM021]
  4. Postdoctoral Science Foundation of China [2012M511032]
  5. Independent Innovation Foundation of Shandong University [IIFS-DU2012T5120, 2012TS123]

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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.

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