WITHDRAWN: Inhibition of CHOP weakens the promotion of chronic intermittent hypoxia on epithelial cells apoptosis via inhibiting PI3K-Akt and NF-κB signaling pathways

Abstract

// Yi-Bin Wang 1, * , Yin Ni 2, * , Ren-Hua Sun 2 , Xiao-Zhou Mou 3 , Fang Han 2 , Qian Li 2 , Hai-Jun Huang 4 , Jing-Quan Liu 2 and Yue-Xing Tu 2 1 Department of Cardiology, Chun’an First People’s Hospital, Zhejiang Provincial People’s Hospital Chun’an Branch, Hangzhou, Zhejiang 311700, China 2 Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China 3 Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medicine College, Hangzhou, Zhejiang 310014, China 4 Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China * These authors contributed equally to this work Correspondence to: Yue-Xing Tu, email: tuyuexing_12@126.com Keywords: chronic intermittent hypoxia; CHOP; PI3K/Akt; NF-κB Received: September 01, 2017 Accepted: November 23, 2017 Published: January 02, 2018 ABSTRACT Objective: To explore the role of transcription factor C/EBP homologous protein (CHOP) on chronic intermittent hypoxia (CIH) epithelial cells and the related molecular mechanism. Results: Expression of CHOP in CIH epithelial cells was significantly higher than the control. CIH promoted the apoptosis of epithelial cells, while transfection of siRNA-CHOP reduced the promotion by CIH. Meanwhile, CIH increased the protein expression cleaved-caspase-3, cleaved-caspase-12 and Bax/Bcl-2. The protein expression of P-PI3K, P-AKT and NF-κB were also markedly increased by CIH, while knockdown of CHOP showed inhibition effect against the increase of P-PI3K, P-AKT and NF-κB by CIH. Conclusion: Inhibition of CHOP could inhibit the promotion of CIH on the apoptotic rate of epithelial cells via inhibition of PI3K/Akt and NF-κB signaling pathway. Methods: In the present study, we used Western blotting was to determine the protein expression of CHOP, interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and cell apoptosis-related factors (cleaved-caspase-3, cleaved-caspase-12, Bcl-2 and Bax) in CIH cells and the control cells. Western blotting and RT-PCR were applied to verify the transfection effect of siRNA-CHOP on epithelial cells. Then the protein expression of activating transcription factor 6 (ATF6), P-PI3K, PI3K, P-AKT, P-AKT and nuclear factor-kappaB (NF-κB) in control or CIH cells was determined after transfection with siRNA-CHOP. Apoptpsis of epithelial cells was determined by flow cytometry assay (FCM) after transfection with siRNA-CHOP.