Rapid uptake of oxidized ascorbate induces loss of cellular glutathione and oxidative stress in liver slices

Jin Hyang Song, Chantelle Simons, Lily Cao, Seon Ho Shin, Murray Hong, Ill Min Chung

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The observation that ascorbate known to retain prooxidant properties induces cell death in a number of immortal cell lines, led us to examine its mechanism and whether it is involved in oxidative stress injury in such asocorbate-enriched tissue cells as hepatocytes. In rat liver homogenates, higher concentrations (1 and 3 mM) of ascorbate suppressed lipid peroxide productions but lower concentrations (0.1 and 0.3 mM) did not. In contrast to the homogenate, ascorbate increased lipid peroxide production in liver slices in a concentration dependant manner. Iso-ascorbate, the epimer of ascorbate did not cause an increase the oxidative stress in liver slices. This differential effect between homogenates and liver slices implies that cellular integrity is required for ascorbate to induce oxidative stress. Wortmannin, an inhibitor of the GLUT (glucose transporter) thought to transport dehydroascorbate into cells, inhibited [14C]- ascorbate uptake and suppressed oxidative stress in liver slices. Wortmannin suppressed that [14C]-ascorbate uptake by GLUT following oxidation to [14C]dehydroascorbate. Taken together, these observations support our hypothesis that ascorbate is oxidized to dehydroascorbate by molecular oxygen in solution (i.e., plasma and culture medium) which is then carried into hepatocytes (via a GLUT) where it is reduced back to ascorbate causing oxidative stress.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalExperimental and Molecular Medicine
Volume35
Issue number2
DOIs
StatePublished - Apr 30 2003
Externally publishedYes

Keywords

  • Ascorbic acid
  • Dehydroascorbic acid
  • Glucose transporter
  • Glutathione
  • Lipid peroxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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