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• W2782398461 abstract "// Jin Tan 1, * , Mengmeng Li 1, * , Xiaofei Meng 1, * , Shuling Song 1, * , Yunyun Fang 1 , Lulu Li 1 , Cong Wang 1 , Yuyang Miao 2 and Qiang Zhang 1 1 Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China 2 Tianjin Medical University, Tianjin, China * These authors contributed equally to this work Correspondence to: Qiang Zhang, email: zhangqiangyulv@163.com Keywords: intermittent hypoxia; autophagy; apoptosis; hippocampal neuron; HIF-1α Received: September 19, 2017      Accepted: December 04, 2017      Published: January 02, 2018 ABSTRACT Unlike the role of autophagy in continuous hypoxia, the role of autophagy in intermittent hypoxia is unclear. To investigate whether autophagy is involved in intermittent hypoxia- caused hippocampal neuronal apoptosis, we studied the activity and action of autophagy in hippocampal neurons after exposure to intermittent hypoxia. We found the expression of autophagy-related proteins and the autolysosome formation were upregulated, and exposure to intermittent hypoxia led to a significant increase in light chain 3 (LC3) turnover and a decrease in SQSTM1/p62 level in hippocampal neurons. Furthermore, accompanying autophagy activation, the level of hypoxia inducible factor-1α (HIF-1α) was increased. Conversely, inhibition of HIF-1α by chemical inhibitor or small interfering RNA (siRNA) downregulated the expression of autophagy-related proteins and blocked autophagy activation. We also found reactive oxygen species (ROS) increased after exposure to intermittent hypoxia, and inhibition of ROS by antioxidants decreased LC3-II expression. What’s more, activation of autophagy by rapamycin exacerbated the apoptosis induced by intermittent hypoxia, whereas inhibition of autophagy by chloroquine or autophagy-related genes siRNA ( Beclin1, Atg5 and Atg7 ) ameliorated intermittent hypoxia-induced apoptosis. Additionally, X-linked inhibitor of apoptosis protein (XIAP), an apoptosis inhibitor protein, was decreased significantly after autophagy activation. Taken together, HIF-1α and ROS-mediated autophagy activation aggravated hippocampal neuronal apoptosis caused by intermittent hypoxia, and the decrease of XIAP might be one of the mechanisms of hippocampal neuronal apoptosis caused by autophagy activation." @default.
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• W2782398461 date "2018-01-02" @default.
• W2782398461 modified "2023-09-22" @default.
• W2782398461 title "Autophagy activation aggravates hippocampal neuronal apoptosis caused by intermittent hypoxia" @default.
• W2782398461 doi "https://doi.org/10.18632/oncotarget.23845" @default.
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