The role of MLKL in Hepatic Ischemia-Reperfusion Injury of Alcoholic Steatotic Livers
| Autor: | Hao Chen, Tara McKeen, Xiaojuan Chao, Allen Chen, Fengyan Deng, Hartmut Jaeschke, Wen-Xing Ding, Hong-Min Ni |
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| Rok vydání: | 2022 |
| Předmět: |
Cell Biology
Applied Microbiology and Biotechnology Mice Inbred C57BL Mice Liver Non-alcoholic Fatty Liver Disease Receptor-Interacting Protein Serine-Threonine Kinases Reperfusion Injury Necroptosis Animals Humans Protein Kinases Molecular Biology Ecology Evolution Behavior and Systematics Developmental Biology |
| Zdroj: | International Journal of Biological Sciences. 18:1096-1106 |
| ISSN: | 1449-2288 |
| Popis: | Alcohol-related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the primary causes of chronic liver disease in western countries. Liver transplantation is currently one of the most efficient approaches to save patients with liver failure, which is often associated with hepatic ischemia-reperfusion (IR) injury. IR injury is exacerbated by hepatic steatosis, yet the mechanism remains elusive. Necroptosis is a form of regulated cell death mediated by receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like (MLKL) protein, which has been implicated in the pathogenesis of ALD and NAFLD. Though necroptosis plays an important role in IR injury of high fat diet - induced steatotic livers, the role of necroptosis in IR injury of ethanol - induced steototic livers has not been investigated. In the present study, we used chronic plus binge alcohol (Gao-binge) feeding followed by IR surgery to investigate IR liver injury with ethanol-associated steatosis. We found that the levels of key necroptotic proteins MLKL and RIP3 increased in alcohol-fed mouse livers. Moreover, we observed increased liver injury after IR in control diet-fed mice, which was further exacerbated by alcohol feeding based on serum alanine aminotransferase (ALT) levels and TUNEL staining of necrotic cells. Hepatic neutrophil infiltration also increased in alcohol-fed mice after IR surgery. However, deletion of |
| Databáze: | OpenAIRE |
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