Liver International · 1997 · 23 citations · 21 references
Life SciencesCell BiologyPharmacologyApoptosisCellular MetabolismMetabolismCellular RespirationCellular Responses To HypoxiaGlycolysis RegulationHepatocellular NecrosisHepatotoxicity MechanismsTricarboxylic Acid CycleAnaerobic GlycolysisGlycolysisGlycolysis Under Anaerobic ConditionsHepatocellular Injury MechanismsHepatocellular Liver InjuryHypoxic Cellular InjuryHypoxic MicroenvironmentMetabolic Injury
The aim of this study was to investigate the mechanism of cytoprotection by glycine against hypoxia-induced hepatocellular injury. Incubation under hypoxic conditions (95% N2 and 5% CO2) for 5 h induced about 50% cell death, but administration of glycine remarkably reduced hepatocellular death without preventing a loss in ATP content. Anaerobic glycolysis generated lactic acid, reducing extracellular pH, but glycine had no effect on changes in extracellular pH. Chloride-channel inhibitors [anthracene-9-carboxylic acid (A9C), furosemide, and strychnine] also significantly reduced hepatocellular death induced by hypoxia. These results suggest that the mechanism of protection by glycine against hypoxic injury is not related to the prevention of ATP depletion or to changes in extracellular pH, but may be due to inhibition of chloride ion influx into the hepatocyte.
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Gregory J. Gores, A. L. Nieminen, B E Wray et al. · Journal of Clinical Investigation · 1989 · 260 citations · Full text