Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway
| Autor: | Hong Jhih Jhuang, Ann-Ping Tsou, Jin Mei Lai, Kuan-Ting Lin, Wei-Hsiang Hsu, Kuen Haur Lee, Feng Sheng Wang, Chen-Kung Chou, Sheau Farn Yeh, Chi Ying F. Huang, Shih-Lan Hsu |
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| Rok vydání: | 2015 |
| Předmět: |
DNA Replication
Hepatitis B virus Carcinoma Hepatocellular Graptopetalum paraguayense PGC-1α 8-Bromo Cyclic Adenosine Monophosphate Biology Crassulaceae medicine.disease_cause Dexamethasone Cell Line Tumor Gene expression HBV medicine Humans Hepatitis B Surface Antigens Plant Extracts Lipogenesis Liver Neoplasms Gluconeogenesis Hep G2 Cells biology.organism_classification Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Virology Gene Expression Regulation Neoplastic Fatty acid synthase Oncology DNA Viral biology.protein Phosphoenolpyruvate carboxykinase Research Paper Signal Transduction Transcription Factors Biomedical sciences |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Hong-Jhih Jhuang 1, * , Wei-Hsiang Hsu 2, * , Kuan-Ting Lin 3 , Shih-Lan Hsu 4 , Feng-Sheng Wang 5 , Chen-Kung Chou 6 , Kuen-Haur Lee 8 , Ann-Ping Tsou 9 , Jin-Mei Lai 7 , Sheau-Farn Yeh 1 , Chi-Ying F. Huang 2, 3, 9 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 2 Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan 3 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 4 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan 5 Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan 6 Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan 7 Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan 8 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 9 Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Jin-Mei Lai, e-mail: jmlai@mail.fju.edu.tw Sheau-Farn Yeh, e-mail: fyeh@ym.edu.tw Chi-Ying F. Huang, e-mail: cyhuang5@ym.edu.tw Keywords: Graptopetalum paraguayense, HBV, Gluconeogenesis, Lipogenesis, PGC-1α Received: November 04, 2014 Accepted: January 06, 2015 Published: February 03, 2015 ABSTRACT PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome. |
| Databáze: | OpenAIRE |
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