title: L-Cysteine promotes the proliferation and differentiation of neural stem cells via the CBS/H₂S pathway.
abstract: 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 β 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.
authors: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors: Z
authors: Z
authors: Wang
authors: D-X
authors: DX
authors: Liu
authors: F-W
authors: FW
authors: Wang
authors: Q
authors: Q
authors: Zhang
authors: Z-X
authors: ZX
authors: Du
authors: J-M
authors: JM
authors: Zhan
authors: Q-H
authors: QH
authors: Yuan
authors: E-A
authors: EA
authors: Ling
authors: A-J
authors: AJ
authors: Hao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013687:Telencephalon / Q000166:cytology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C112418:32-ascomycinyloxyacetic acid; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D003541:Cystathionine beta-Synthase; D001973:Bromodeoxyuridine; D003545:Cysteine; D016559:Tacrolimus; D006862:Hydrogen Sulfide