Knockout of the Gsta4 Gene in Male Mice Leads to an Altered Pattern of Hepatic Protein Carbonylation and Enhanced Inflammation Following Chronic Consumption of an Ethanol Diet
| Autor: | David J. Orlicky, Kyle Meredith, Dennis R. Petersen, Kelly E. Mercer, Casey F. Pulliam, Martin J. J. Ronis, Colin T. Shearn, Laura Saba, Kim Brint Pedersen |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Alcoholic liver disease Mice 129 Strain Protein Carbonylation Medicine (miscellaneous) Toxicology Article Protein Structure Secondary GSTA4 Lipid peroxidation Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Liver Diseases Alcoholic Glutathione Transferase Inflammation Mice Knockout Liver injury Ethanol 030102 biochemistry & molecular biology Chemistry medicine.disease Psychiatry and Mental health 030104 developmental biology Endocrinology Liver Hepatic stellate cell Tumor necrosis factor alpha Steatosis |
| Zdroj: | Alcoholism: Clinical and Experimental Research. 42:1192-1205 |
| ISSN: | 0145-6008 |
| Popis: | BACKGROUND: Glutathione-S-transferase A4-4 (GSTA4) is a key enzyme for removal of toxic lipid peroxidation products such as 4-hydroxynonenal (4-HNE). In the current study, we examined the potential role of GSTA4 on protein carbonylation and progression of alcoholic liver disease (ALD) by examining the development of liver injury in male wild type SV/J mice (WT) and SV/J mice lacking functional GSTA4 (GSTA4(−/−) mice). METHODS: Adult male WT and GSTA4(−/−) mice were fed chow (N = 10-12) or high fat Lieber-DeCarli liquid diets containing up to 28% calories as ethanol (EtOH) (N = 18-20) for 116 days. At the end of the study, half of the ethanol-fed mice were acutely challenged with an ethanol binge (3 g/kg given intragastrically) 12 hours before sacrifice. Carbonylation of liver proteins was assessed by immunohistochemical staining for 4-HNE adduction and by comprehensive liquid chromatography tandem mass spectrometry, LC-MS/MS, of purified carbonylated proteins. RESULTS: Chronic EtOH intake significantly increased hepatic 4-HNE adduction and protein carbonylation, including carbonylation of ribosomal proteins. EtOH intake also resulted in steatosis and increased serum ALTs. Hepatic infiltration with B-cells, T-cells, and neutrophils and mRNA expression of pro-inflammatory cytokines TNFα and IFNγ was modest in WT mice. However, an ethanol binge increased hepatic necrosis, hepatic cell proliferation and expression of TNFα mRNA (P |
| Databáze: | OpenAIRE |
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