文献类型：期刊文献

英文题名：Hypobaric Hypoxia Increased Autophagy and Apoptosis in PC12 Rat Pheochromocytoma Cells More Than Normobaric Hypoxia

作者：Yin, Jiaojiao[1,2,3];Wang, Yuhang[2];Li, Bing[3];Hu, Xiaoyan[1];Ma, Yao[1];Zhang, Chong[1];Ha, Xiaoqin[2,3];Wang, Linyan[1];Pan, Yaozhu[3]

第一作者：Yin, Jiaojiao;尹晶晶

通信作者：Pan, YZ[1];Wang, LY[2]

机构：[1]Gansu Prov Matern & Child Care Hosp, Dept Clin Lab, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou, Peoples R China;[3]940th Hosp Chinese Peoples Liberat Army Joint Supp, 333 Binhe Middle Rd, Lanzhou 730050, Peoples R China

第一机构：Gansu Prov Matern & Child Care Hosp, Dept Clin Lab, Lanzhou, Peoples R China

通信机构：[1]corresponding author), 940th Hosp Chinese Peoples Liberat Army Joint Supp, 333 Binhe Middle Rd, Lanzhou 730050, Peoples R China;[2]corresponding author), Gansu Prov Matern & Childcare Hosp, 143 Qilihe North St, Lanzhou 730050, Gansu, Peoples R China.

年份：2025

外文期刊名：HIGH ALTITUDE MEDICINE & BIOLOGY

收录：;Scopus(收录号：2-s2.0-85217531348);WOS:【SCI-EXPANDED(收录号:WOS:001418047900001)】；

基金：This work was supported by the Natural Science Foundation of Gansu Province, China (Grant 22JR5RA716)

语种：英文

外文关键词：acute mountain sickness; hypobaric hypoxia; normobaric hypoxia; autophagy; apoptosis

摘要：Purpose: Currently, in vitro studies have focused on hypoxia injury in acute mountain sickness (AMS), but little effort has been made to assess the effects of hypobaric hypoxia. AMS is a neurological disorder, and rat pheochromocytoma (PC12) cells are a model to study neuronal survival and apoptosis. Here, we developed a novel cell culture method that mimics hypobaric hypoxia at high attitude and compared the effects of hypobaric hypoxia and normobaric hypoxia on autophagy and apoptosis of PC12 cells. Methods: PC12 cells were cultured under normal conditions, normobaric hypoxia, and hypobaric hypoxia. Autophagy was observed by transmission electron microscopy and immunofluorescence microscopy. The hypoxia-inducible factor1-alpha (HIF1-alpha), LC3, caspase-3, and cleaved caspase-3 expression levels were determined by Western blot. Results: The cell culture chamber mimicking hypobaric hypoxia at high attitude perfectly maintained the air pressure at 41.1 kPa and the oxygen density at 1% (PO2 around 3.08 mmHg). Hypobaric hypoxic treatment of PC12 cells at 0, 4, 8, 16, 24, and 48 hours resulted in an increase in HIF1-alpha and LC3II protein levels, and the ratio of HIF1-alpha/actin and LC3II/actin both peaked at 16 hours (p < 0. 01) when the cell viability was 88.02%. There was a 1.5-fold increase in LC3II expression, a 2-fold increase in LC3B-positive spots, and an increase in autophagosome accumulation at hypobaric hypoxia compared to PC12 cells at normobaric hypoxia for 16 hours (p < 0.001). Interestingly, the promotion of autophagy (coculture with rapamycin or 3-MA) in PC12 cells under normobaric hypoxia reduced cleaved caspase-3 expression (the ratio of cleaved caspase-3/caspase-3 decreased, p < 0.01). However, under hypobaric hypoxia, the promotion of autophagy inversely increased cleaved caspase-3 (the ratio of cleaved caspase-3/caspase-3 increased, p < 0.01), and the inhibition of autophagy (hydroxychloroquine [HCQ] coculture) decreased cleaved caspase-3 (the ratio of cleaved caspase-3/caspase-3 decreased, p < 0.01). Conclusions: Compared with normobaric hypoxia cells, hypobaric hypoxia cells cultured in vitro exhibited increased autophagy and apoptosis.