Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes
Hepatitis B virus is one of the main causes of hepatitis and hepatocellular carcinoma (HCC). Hepatitis B virus-encoded X protein (HBx) has been shown to be involved in many aspects of the pathogenicity of liver diseases. Orexin A is a small peptide produced in the hippocampus. Orexin A and its recep...
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Taylor & Francis Group
2019-12-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1614014 |
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| author | Li Wang Tao He Baishun Wan Xiaoqian Wang Ling Zhang |
| author_facet | Li Wang Tao He Baishun Wan Xiaoqian Wang Ling Zhang |
| author_sort | Li Wang |
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| description | Hepatitis B virus is one of the main causes of hepatitis and hepatocellular carcinoma (HCC). Hepatitis B virus-encoded X protein (HBx) has been shown to be involved in many aspects of the pathogenicity of liver diseases. Orexin A is a small peptide produced in the hippocampus. Orexin A and its receptor have become important therapeutic targets for certain metabolic disorders. In this study, we show that orexin A has a protective role against HBx-induced cytotoxicity and inflammation in hepatocytes. The ectopic expression of HBx in hepatocytes reduces orexin A receptor 1 (OX1R) expression. When orexin A is added to the cells, it mitigates HBx-induced oxidative stress indicator 4-hydroxynonenal (4-HNE) and reactive oxygen species (ROS) as well the NADPH subunit NADPH oxidase 4 (NOX-4). Orexin A also ameliorates HBx-mediated mitochondrial membrane potential and adenosine triphosphate (ATP) reduction. Moreover, orexin A significantly inhibits HBx-induced production of pro-inflammatory cytokines including interleukin 8 (IL-8), tumour necrosis factor α (TNF-α) and chemokine ligand 2 (CXCL2). The presence of orexin A ameliorates HBx-induced lactate dehydrogenase (LDH) release, indicating that it could protect hepatocytes from cytotoxicity. Mechanistically, we found that orexin A suppresses c-Jun N-terminal kinase (JNK) phosphorylation, accumulation of nuclear factor-κB (NF-κB) protein p65 in nuclei, and NF-κB promoter activity, suggesting that orexin A suppresses JNK and NF-κB pathway activation. In conclusion, our study demonstrates that orexin A peptide possesses a protective role against HBx-mediated cytotoxicity and inflammation in hepatocytes. |
| format | Article |
| id | doaj-art-0a779124b3cd4bafbed74854625191d5 |
| institution | Kabale University |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Taylor & Francis Group |
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| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-0a779124b3cd4bafbed74854625191d52025-08-20T03:51:08ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014712003200910.1080/21691401.2019.1614014Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytesLi Wang0Tao He1Baishun Wan2Xiaoqian Wang3Ling Zhang4Department of Hepatopancreatobiliary Surgery, He’nan Tumor Hospital, Affiliated to Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, He’nan Tumor Hospital, Affiliated to Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, He’nan Tumor Hospital, Affiliated to Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, He’nan Tumor Hospital, Affiliated to Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, He’nan Tumor Hospital, Affiliated to Zhengzhou University, Zhengzhou, ChinaHepatitis B virus is one of the main causes of hepatitis and hepatocellular carcinoma (HCC). Hepatitis B virus-encoded X protein (HBx) has been shown to be involved in many aspects of the pathogenicity of liver diseases. Orexin A is a small peptide produced in the hippocampus. Orexin A and its receptor have become important therapeutic targets for certain metabolic disorders. In this study, we show that orexin A has a protective role against HBx-induced cytotoxicity and inflammation in hepatocytes. The ectopic expression of HBx in hepatocytes reduces orexin A receptor 1 (OX1R) expression. When orexin A is added to the cells, it mitigates HBx-induced oxidative stress indicator 4-hydroxynonenal (4-HNE) and reactive oxygen species (ROS) as well the NADPH subunit NADPH oxidase 4 (NOX-4). Orexin A also ameliorates HBx-mediated mitochondrial membrane potential and adenosine triphosphate (ATP) reduction. Moreover, orexin A significantly inhibits HBx-induced production of pro-inflammatory cytokines including interleukin 8 (IL-8), tumour necrosis factor α (TNF-α) and chemokine ligand 2 (CXCL2). The presence of orexin A ameliorates HBx-induced lactate dehydrogenase (LDH) release, indicating that it could protect hepatocytes from cytotoxicity. Mechanistically, we found that orexin A suppresses c-Jun N-terminal kinase (JNK) phosphorylation, accumulation of nuclear factor-κB (NF-κB) protein p65 in nuclei, and NF-κB promoter activity, suggesting that orexin A suppresses JNK and NF-κB pathway activation. In conclusion, our study demonstrates that orexin A peptide possesses a protective role against HBx-mediated cytotoxicity and inflammation in hepatocytes.https://www.tandfonline.com/doi/10.1080/21691401.2019.1614014HBV protein x (HBx)orexin AhepatocytescytotoxicityinflammationJNK |
| spellingShingle | Li Wang Tao He Baishun Wan Xiaoqian Wang Ling Zhang Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes Artificial Cells, Nanomedicine, and Biotechnology HBV protein x (HBx) orexin A hepatocytes cytotoxicity inflammation JNK |
| title | Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes |
| title_full | Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes |
| title_fullStr | Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes |
| title_full_unstemmed | Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes |
| title_short | Orexin A ameliorates HBV X protein-induced cytotoxicity and inflammatory response in human hepatocytes |
| title_sort | orexin a ameliorates hbv x protein induced cytotoxicity and inflammatory response in human hepatocytes |
| topic | HBV protein x (HBx) orexin A hepatocytes cytotoxicity inflammation JNK |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1614014 |
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