PMID- 30203298 OWN - NLM STAT- MEDLINE DCOM- 20181218 LR - 20181218 IS - 1559-1166 (Electronic) IS - 0895-8696 (Print) IS - 0895-8696 (Linking) VI - 66 IP - 2 DP - 2018 Oct TI - HIF-1alpha/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning. PG - 238-250 LID - 10.1007/s12031-018-1162-7 [doi] AB - Hypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic brain injury, and one mechanism explaining this effect may involve the upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous protective mechanism against hypoxic/ischemic injury, is correlated with the activation of the HIF-1alpha/Beclin1 signaling pathway. Based on previous studies, we hypothesize that the protective role of HPC may involve autophagy occurring via activation of the HIF-1alpha/Beclin1 signaling pathway. To test this hypothesis, we evaluated the effects of HPC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptosis and autophagy in SH-SY5Y cells. HPC significantly attenuated OGD/R-induced apoptosis, and this effect was suppressed by the autophagy inhibitor 3-methyladenine and mimicked by the autophagy agonist rapamycin. In control SH-SY5Y cells, HPC upregulated the expression of HIF-1alpha and downstream molecules such as BNIP3 and Beclin1. Additionally, HPC increased the LC3-II/LC3-I ratio and decreased p62 levels. The increase in the LC3-II/LC3-I ratio was inhibited by the HIF-1alpha inhibitor YC-1 or by Beclin1-short hairpin RNA (shRNA). In OGD/R-treated SH-SY5Y cells, HPC also upregulated the expression levels of HIF-1alpha, BNIP3, and Beclin1, as well as the LC3-II/LC3-I ratio. Furthermore, YC-1 or Beclin1-shRNA attenuated the HPC-mediated cell viability in OGD/R-treated cells. Taken together, our results demonstrate that HPC protects SH-SY5Y cells against OGD/R via HIF-1alpha/Beclin1-regulated autophagy. FAU - Lu, Na AU - Lu N AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. AD - Key Laboratory for the Brain Research of Henan Province, Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, 453003, Henan, People's Republic of China. FAU - Li, Xingxing AU - Li X AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Tan, Ruolan AU - Tan R AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - An, Jing AU - An J AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Cai, Zhenlu AU - Cai Z AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Hu, Xiaoxuan AU - Hu X AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Wang, Feidi AU - Wang F AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Wang, Haoruo AU - Wang H AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. FAU - Lu, Chengbiao AU - Lu C AD - Key Laboratory for the Brain Research of Henan Province, Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, 453003, Henan, People's Republic of China. FAU - Lu, Haixia AU - Lu H AD - Institute of Neurobiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China. hxl01@mail.xjtu.edu.cn. LA - eng GR - 81771517/National Natural Science Foundation of China(NSFC)/ GR - 14A310009/Science and Technology Key Research Project Grant from Department of Education of Henan Province/ GR - 81571205/National Natural Science Foundation of China/ PT - Journal Article DEP - 20180910 PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (BECN1 protein, human) RN - 0 (BNIP3 protein, human) RN - 0 (Beclin-1) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Apoptosis MH - *Autophagy MH - Beclin-1/genetics/*metabolism MH - Cell Hypoxia MH - Cell Line, Tumor MH - Glucose/deficiency MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism MH - Membrane Proteins/genetics/metabolism MH - Neurons/*metabolism MH - Oxygen/*metabolism MH - Proto-Oncogene Proteins/genetics/metabolism PMC - PMC6182618 OTO - NOTNLM OT - Autophagy OT - Beclin1 OT - HIF-1alpha OT - Hypoxic preconditioning OT - Oxygen-glucose deprivation/reperfusion OT - SH-SY5Y cells COIS- The authors declare that they have no conflicts of interest. EDAT- 2018/09/12 06:00 MHDA- 2018/12/19 06:00 PMCR- 2018/09/10 CRDT- 2018/09/12 06:00 PHST- 2018/05/23 00:00 [received] PHST- 2018/08/20 00:00 [accepted] PHST- 2018/09/12 06:00 [pubmed] PHST- 2018/12/19 06:00 [medline] PHST- 2018/09/12 06:00 [entrez] PHST- 2018/09/10 00:00 [pmc-release] AID - 10.1007/s12031-018-1162-7 [pii] AID - 1162 [pii] AID - 10.1007/s12031-018-1162-7 [doi] PST - ppublish SO - J Mol Neurosci. 2018 Oct;66(2):238-250. doi: 10.1007/s12031-018-1162-7. Epub 2018 Sep 10.