Modification of glycolysis affects cell sensitivity to apoptosis induced by oxidative stress and mediated by mitochondria

Dae Won Jeong, Tae Soo Kim, Il Taeg Cho, Ick Young Kim

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The effect of alteration of the glycolytic pathway on cell damage induced by oxidative stress was investigated with dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cells that either overexpress cytosolic glycerol-3-phosphate dehydrogenase (CHO/cGPDH cells) or are depleted of the A subunit of lactate dehydrogenase as a result of anti-sense RNA expression (CHO/anti-LDH cells). The extent of oxidative phosphorylation in CHO/anti-LDH and CHO/cGPDH cells was increased and decreased, respectively, relative to that in parental CHO cells, as revealed by measurement of the intracellular content of ATP, the rate of cellular O2 consumption, the mitochondrial membrane potential (ΔΨm), and the generation of reactive oxygen species. The sensitivity of these cell lines to cell death induced by the exogenous oxidant tert-butyl hydroperoxide decreased according to the rank order CHO/anti-LDH > CHO > CHO/cGPDH. Exogenous pyruvate markedly increased the sensitivity of CHO/cGPDH cells to oxidant-induced death. The differences among the three cell lines in susceptibility to oxidant-induced death were reflected in the proportion of oxidant-treated cells with a subdiploid DNA content, with a collapsed ΔΨm, and with cytochrome c in the cytosol, indicating that death was mediated by apoptosis. These results demonstrate that the influx of respiratory substrate into mitochondria is an important determinant of cell sensitivity to oxidant-induced apoptosis.

Original languageEnglish
Pages (from-to)984-991
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume313
Issue number4
DOIs
Publication statusPublished - 2004 Jan 23

Keywords

  • Apoptosis
  • Glycolysis
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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