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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Pyruvate Protection against Endothelial Cytotoxicity Induced by Blockade of Glucose Uptake

  • Chung, Se-Jin (Division of Life Sciences and Silver Biotechnology Research Center, Hallym University) ;
  • Lee, Se-Hee (Division of Life Sciences and Silver Biotechnology Research Center, Hallym University) ;
  • Lee, Yong-Jin (Division of Life Sciences and Silver Biotechnology Research Center, Hallym University) ;
  • Park, Hyoung-Sook (Department of Environmental Engineering, Hanseo University) ;
  • Bunger, Rolf (Physiology and Molecular/Cell Biology, Uniformed Services University of Health Sciences) ;
  • Kang, Young-Hee (Division of Life Sciences and Silver Biotechnology Research Center, Hallym University)
  • Published : 2004.03.31
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Abstract

We have previously demonstrated that the redox reactant pyruvate prevents apoptosis in the oxidant model of bovine pulmonary artery endothelial cells (BPAEC), and that the anti-apoptotic mechanism of pyruvate is mediated in part via the mitochondrial matrix compartment. However, cytosolic mechanisms for the cytoprotective feature of pyruvate remain to be elucidated. This study investigated the pyruvate protection against endothelial cytotoxicity when the glycolysis inhibitor 2-deoxy-D-glucose (2DG) was applied to BPAEC. Millimolar 2DG blocked the cellular glucose uptake in a concentration- and time-dependent manner with >85% inhibition at $\geq$5 mM within 24 h. The addition of 2DG evoked BPAEC cytotoxicity with a substantial increase in lipid peroxidation and a marked decrease in intracellular total glutathione. Exogenous pyruvate partially prevented the 2DG-induced cell damage with increasing viability of BPAEC by 25-30%, and the total glutathione was also modestly increased. In contrast, 10 mM L-lactate, as a cytosolic reductant, had no effect on the cytotoxicity and lipid peroxidation that are evoked by 2DG. These results suggest that 2DG toxicity may be a consequence of the diminished potential of glutathione antioxidant, which was partially restored by exogenous pyruvate but not L-lactate. Therefore, pyruvate qualifies as a cytoprotective agent for strategies that attenuate the metabolic dysfunction of the endothelium, and cellular glucose oxidation is required for the functioning of the cytosolic glutathione/NADPH redox system.

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References

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