Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia

Lin YN, Lan XF, Liu ZR, Yan YR, Zhou JP, Li N, Sun XW, Li QY
2019 Nature and Science of Sleep  
Ying Ni Lin,1,2,* Xiao Fei Lan,1,3,* Zhuo Ran Liu,4,* Ya Ru Yan,1,2 Jian Ping Zhou,1,2 Ning Li,1,2 Xian Wen Sun,1,2 Qing Yun Li1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China; 2Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China; 3Department of Respiratory Medicine, Shanghai Tongren Hospital,
more » ... Jiao Tong University School of Medicine, Shanghai 200335, People's Republic of China; 4Department of Thyroid and Vascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of ChinaTel +86-21-64370045Email liqingyun68@hotmail.comPurpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure.Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting.Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downst [...]
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