Mouse genetic background contributes to hepatocyte susceptibility to Fas-mediated apoptosis
| Autor: | M. Bishr Omary, Daniel A. Portney, Min-Jung Park, Sujith V.W. Weerasinghe |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fas Ligand Protein Cell Culture Techniques Apoptosis Protein degradation Fas ligand Mice 03 medical and health sciences 0302 clinical medicine medicine Animals fas Receptor Molecular Biology Caspase Acetaminophen bcl-2-Associated X Protein Caspase 7 Caspase 8 Mice Inbred C3H biology Caspase 3 Autophagy Cell Biology Fas receptor Molecular biology Mice Inbred C57BL bcl-2 Homologous Antagonist-Killer Protein 030104 developmental biology medicine.anatomical_structure Liver Cell culture Hepatocyte Hepatocytes biology.protein Brief Reports 030211 gastroenterology & hepatology Genetic Background BH3 Interacting Domain Death Agonist Protein Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e15-06-0423 |
| Popis: | Mouse strain–dependent selective loss of apoptosis enzymes, with consequent decrease in susceptibility to apoptosis, occurs upon short-term hepatocyte culture and in vivo. These susceptibility differences likely reflect genetic modifiers that provide resistance or predisposition to hepatocyte death. Liver disease progression is modulated by genetic modifiers in mouse strains and across human races and ethnicities. We hypothesized that hepatocyte culture duration and genetic background regulate hepatocyte susceptibility to apoptosis. Hepatocytes were isolated from FVB/N, C57BL/6, and C3H/He mice and cultured or treated with Fas ligand or acetaminophen after different culture times. Protein and mRNA expressions of Fas receptor, caspases-3/7/8, and Bak/Bax/Bid proteins were determined. FVB/N hepatocytes manifested rapid decreases of caspases-3/7 but not caspase-8 as culture time increased, which paralleled decreased susceptibility to apoptosis. Some changes were also found in Fas-receptor and Bak, Bax, and Bid proteins; caspase mRNA decreases were also noted. Caspase protein degradation was partially reversed by lysosomal protease but not proteasome or autophagy inhibitors. C57BL/6 and FVB/N hepatocytes behaved similarly in their limited susceptibility to apoptosis, whereas C3H/He hepatocytes show limited alterations in caspases, with consequent increased susceptibility to apoptosis. Similarly, C3H/He mice were more susceptible than C57BL/6 and FVB/N mice to Fas-mediated liver injury. Therefore there are significant mouse strain–dependent differences in susceptibility to apoptosis and selective loss of caspases upon short-term hepatocyte culture, with consequent decrease in susceptibility to apoptosis. These differences likely reflect genetic modifiers that provide resistance or predisposition to hepatocyte death. |
| Databáze: | OpenAIRE |
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