Chronic hepatitis B is a disease of the liver that can progress to cirrhosis and liver cancer. The HBx (hepatitis B virus X) protein of hepatitis B virus is a multifunctional regulator that induces ER (endoplasmic reticulum) stress by previously unknown mechanisms. ER stress plays a critical role in inflammatory induction and COX2 (cyclo-oxygenase 2) is an important mediator of this inflammation. In the present study, we demonstrate the molecular mechanisms of HBx on induction of ER stress and COX2 expression. In addition, HBx reduced expression of enzymes which are involved in mitochondrial β-oxidation of fatty acids and the mitochondrial inner membrane potential. The reduction in intracellular ATP levels by HBx induced the unfolded protein response and COX2 expression through the eIF2α (eukaryotic initiation factor 2α)/ATF4 (activating transcription factor 4) pathway. We confirmed that ATF4 binding to the COX2 promoter plays a critical role in HBx-mediated COX2 induction. The results of the present study suggest that HBV infection contributes to induction of hepatic inflammation through dysfunction of cellular organelles including the ER and mitochondria.
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Research Article|
March 29 2011
Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4
Hyun Kook Cho;
Hyun Kook Cho
*Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea
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Kyu Jin Cheong;
Kyu Jin Cheong
†Pre-university Preparation Course, High school course, Pusan National University, Busan 609-735, South Korea
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Hye Young Kim;
Hye Young Kim
*Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea
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JaeHun Cheong
JaeHun Cheong
1
*Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea
†Pre-university Preparation Course, High school course, Pusan National University, Busan 609-735, South Korea
‡Mitochondrial Hub Regulation Center, 3-1 Dongdaesin-Dong, Seo-Gu, Busan 602-714, South Korea
1To whom correspondence should be addressed (email molecule85@pusan.ac.kr).
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Publisher: Portland Press Ltd
Received:
December 09 2010
Accepted:
January 19 2011
Accepted Manuscript online:
January 19 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 435 (2): 431–439.
Article history
Received:
December 09 2010
Accepted:
January 19 2011
Accepted Manuscript online:
January 19 2011
Citation
Hyun Kook Cho, Kyu Jin Cheong, Hye Young Kim, JaeHun Cheong; Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4. Biochem J 15 April 2011; 435 (2): 431–439. doi: https://doi.org/10.1042/BJ20102071
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