Peroxynitrite enhances self-renewal, proliferation and neuronal differentiation of neural stem/progenitor cells through activating HIF-1α and Wnt/β-catenin signaling pathway
Autor: | Jinghan Feng, Xingmiao Chen, Dan Yang, Tingting Yan, Binghua Zhou, Tao Peng, Chong Gao, Jiangang Shen, Hansen Chen, Hao Wu |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Neurogenesis Endogeny Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neural Stem Cells Peroxynitrous Acid Physiology (medical) Animals Progenitor cell Wnt Signaling Pathway Cells Cultured reproductive and urinary physiology Cell Proliferation chemistry.chemical_classification Reactive oxygen species Wnt signaling pathway Cell Differentiation Cell sorting Hypoxia-Inducible Factor 1 alpha Subunit Rats Cell biology 030104 developmental biology nervous system chemistry Hypoxia-Ischemia Brain Signal transduction 030217 neurology & neurosurgery Peroxynitrite |
Zdroj: | Free Radical Biology and Medicine. 117:158-167 |
ISSN: | 0891-5849 |
DOI: | 10.1016/j.freeradbiomed.2018.02.011 |
Popis: | Hypoxic/ischemic stimulation could mediate growth and differentiation of neural stem/progenitor cells (NSCs) into mature neurons but its underlying mechanisms are largely unclear. Peroxynitrite formation is considered as a crucial pathological process contributing to cerebral ischemia-reperfusion injury. In the present study, we tested the hypothesis that peroxynitrite at low concentration could function as redox signaling to promote the growth of NSCs under hypoxic/ischemic conditions. Increased NSCs proliferation was accompanied by peroxynitrite production in the rat brains with 1 h of ischemia plus 7 days of reperfusion in vivo. Cell sorting experiments revealed that endogenous peroxynitrite level affected the capacity of proliferation and self-renewal in NSCs in vitro. Hypoxia stimulated peroxynitrite production and promoted NSCs self-renewal, proliferation and neuronal differentiation whereas treatments of peroxynitrite decomposition catalysts (PDCs, FeTMPyP and FeTPPS) blocked the changes in NSCs self-renewal, proliferation and neuronal differentiation. Exogenous peroxynitrite treatment revealed similar effects to promote NSCs proliferation, self-renewal and neuronal differentiation. Furthermore, the neurogenesis-promoting effects of peroxynitrite were partly through activating HIF-1α correlated with enhanced Wnt/β-catenin signaling pathway. In conclusion, peroxynitrite could be a cellular redox signaling for promoting NSCs proliferation, self-renewal and neuronal differentiation and peroxynitrite production could contribute to neurogenesis in ischemic/hypoxic NSCs. |
Databáze: | OpenAIRE |
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