Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: protection by betaine
| Autor: | David D. Rogers, Gerri L. Siford, Kusum K. Kharbanda, Harriet C. Beckenhauer, Mark E. Mailliard, Dean J. Tuma, Michael F. Sorrell, Anthony J. Barak |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Adenosine Apoptosis DNA Fragmentation Biology Biochemistry Methylation chemistry.chemical_compound Betaine Internal medicine medicine Animals Rats Wistar Cells Cultured Pharmacology Liver injury Methionine Ethanol Caspase 3 medicine.disease S-Adenosylhomocysteine Rats Endocrinology medicine.anatomical_structure chemistry Cytoprotection Hepatocyte Caspases Hepatocytes Intracellular medicine.drug |
| Zdroj: | Biochemical pharmacology. 70(12) |
| ISSN: | 0006-2952 |
| Popis: | Previous studies from our laboratory have shown that ethanol consumption results in an increase in hepatocellular S-adenosylhomocysteine levels. Because S-adenosylhomocysteine is a potent inhibitor of methylation reactions, we propose that increased intracellular S-adenosylhomocysteine levels could be a major contributor to ethanol-induced pathologies. To test this hypothesis, hepatocytes isolated from rat livers were grown on collagen-coated plates in Williams’ medium E containing 5% FCS and exposed to varying concentrations of adenosine in order to increase intracellular S-adenosylhomocysteine levels. We observed increases in caspase-3 activity following exposure to adenosine. This increase in caspase activity correlated with increases in intracellular S-adenosylhomocysteine levels and DNA hypoploidy. The adenosine-induced changes could be significantly attenuated by betaine administration. The mechanism of betaine action appeared to be via the methylation reaction catalyzed by betaine-homocysteine-methyltransferase. To conclude, our results indicate that the elevation of S-adenosylhomocysteine levels in the liver by ethanol is a major factor in altering methylation reactions and in increasing apoptosis in the liver. We conclude that ethanol-induced alteration in methionine metabolic pathways may play a crucial role in the pathologies associated with alcoholic liver injury and that betaine administration may have beneficial therapeutic effects. |
| Databáze: | OpenAIRE |
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