Antagonism of RIP1 using necrostatin-1 (Nec-1) ameliorated damage and inflammation of HBV X protein (HBx) in human normal hepatocytes
| Autor: | Linsen Xie, Yongjie Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Artificial Cells, Nanomedicine, and Biotechnology, Vol 47, Iss 1, Pp 1194-1199 (2019) |
| Druh dokumentu: | article |
| ISSN: | 21691401 2169-141X 2169-1401 |
| DOI: | 10.1080/21691401.2019.1575231 |
| Popis: | Hepatitis B virus X protein (HBx), encoded by the hepatitis B virus (HBV) genome, plays a pivotal in mediating pathogenicity in liver diseases. However, the underlying mechanisms are still needed to be elucidated. Receptor-interacting protein 1 (RIP1) has been identified as a serine/threonine kinase with various biological functions in cell fate, proliferation, and death. In the current study, we found that overexpression of HBx in LO2 human normal hepatocytes increased the expression of RIP1. Importantly, our results indicate that blockage of RIP1 using its specific antagonist necrostatin-1 (Nec-1) ameliorated HBx-induced oxidative stress by mitigating the production of ROS and Nox-4 expression. Also, the presence of Nec-1 improved HBx-induced mitochondrial dysfunction by increasing MMP. Importantly, we found that Nec-1 could inhibit the production of pro-inflammatory cytokines IL-6, IL-8, and CXCL2 as well as the secretion of HMGB1. Mechanistically, we found that Nec-1 treatment suppressed the activation of the JNK/AP-1 and NF-κB signalling pathways. Our findings implicated a novel biological function of RIP1 in HBx-induced cytotoxicity and inflammation in human normal hepatocytes. Antagonism of RIP1 might be a potential therapeutic approach for the treatment of HBV-associated liver diseases. |
| Databáze: | Directory of Open Access Journals |
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