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Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.
Li, Jian; Gong, Sheng-Hui; He, Yun-Ling; Cao, Yan; Chen, Ying; Huang, Guang-Hai; Wang, Yu-Fei; Zhao, Ming; Cheng, Xiang; Zhou, Yan-Zhao; Zhao, Tong; Zhao, Yong-Qi; Fan, Ming; Wu, Hai-Tao; Zhu, Ling-Ling; Wu, Li-Ying.
Afiliação
  • Li J; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
  • Gong SH; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • He YL; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Cao Y; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
  • Chen Y; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
  • Huang GH; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Wang YF; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
  • Zhao M; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Cheng X; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Zhou YZ; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Zhao T; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Zhao YQ; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Fan M; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Wu HT; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Zhu LL; Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, People's Republic of China.
  • Wu LY; Department of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, People's Republic of China.
Stem Cells ; 41(1): 77-92, 2023 01 30.
Article em En | MEDLINE | ID: mdl-36208284
Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neurais / Proteínas de Membrana Limite: Humans Idioma: En Revista: Stem Cells Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neurais / Proteínas de Membrana Limite: Humans Idioma: En Revista: Stem Cells Ano de publicação: 2023 Tipo de documento: Article