Hepatitis B virus X protein sensitizes HL-7702 cells to oxidative stress-induced apoptosis through modulation of the mitochondrial permeability transition pore

Gao,Wen-Yu; Li,Dan; Cai,De-En; Huang,Xiao-Yun; Zheng,Bi-Yun; Huang,Yue-Hong; Chen,Zhi-Xin; Wang,Xiao-Zhong

doi:10.3892/or.2016.5225

Hepatitis B virus X protein sensitizes HL-7702 cells to oxidative stress-induced apoptosis through modulation of the mitochondrial permeability transition pore

Authors:
- Wen-Yu Gao
- Dan Li
- De-En Cai
- Xiao-Yun Huang
- Bi-Yun Zheng
- Yue-Hong Huang
- Zhi-Xin Chen
- Xiao-Zhong Wang
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Affiliations: Department of Gastroenterology, Fujian Medical University Union Hospital, Fujian 350001, P.R. China, Graduate School, Fujian Medical University, Fujian 350001, P.R. China
Published online on: November 7, 2016 https://doi.org/10.3892/or.2016.5225
Pages: 48-56
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and cancer. Among the pathogenic factors of HBV, HBV X protein (HBx) is attracting increased attention. Although it is documented that HBx is a multifunctional regulator that modulates cell inflammation and apoptosis, the exact mechanism remains controversial. In the present study, we explored the effect of HBx on oxidative stress-induced apoptosis in normal liver cell line, HL-7702. Our results showed that the existence of HBx affected mitochondrial biogenesis by modulating the opening of the mitochondrial permeability transition pore (MPTP). Notably, this phenomenon was associated with a pronounced translocation of Bax from the cytosol to the mitochondria during the period of exposure to oxidative stress with a release of cytochrome c and activation of cleaved caspase-3 and PARP. Moreover, MPTP blockage with cyclosporin A prevented the translocation of Bax, and inhibited oxidative stress-induced apoptotic killing in the HBx-expressing HL-7702 cells. Our findings suggest that HBx exhibits pro-apoptotic effects upon normal liver cells following exposure to oxidative stress by modulating the MPTP gateway.

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