Alterations in intracellular thiol homeostasis during the metabolism of menadione by isolated rat hepatocytes

Donato Di Monte, David Ross, Giorgio Bellomo, Lena Eklöw, Sten Orrenius

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

The effects of menadione (2-methyl-1,4-naphthoquinone) metabolism on intracellular soluble and protein-bound thiols were investigated in freshly isolated rat hepatocytes. Menadione was found to cause a dose-dependent decrease in intracellular glutathione (GSH) level by three different mechanisms: (a) Oxidation of GSH to glutathione disulfide (GSSG) accounted for 75% of the total GSH loss; (b) About 15% of the cellular GSH reacted directly with menadione to produce a GSH-menadione conjugate which, once formed, was excreted by the cells into the medium; (c) A small amount of GSH (~10%) was recovered by reductive treatment of cell protein with NaBH4, indicating that GSH-protein mixed disulfides were also formed as a result of menadione metabolism. Incubation of hepatocytes with high concentrations of menadione (>200 μm) also induced a marked decrease in protein sulfhydryl groups; this was due to arylation as well as oxidation. Binding of menadione represented, however, a relatively small fraction of the total loss of cellular sulfhydryl groups, since it was possible to recover about 80% of the protein thiols by reductive treatments which did not affect protein binding. This suggests that the loss of protein sulfhydryl groups, like that of GSH, was mainly a result of oxidative processes occurring within the cell during the metabolism of menadione.

Lingua originaleInglese
pagine (da-a)334-342
Numero di pagine9
RivistaArchives of Biochemistry and Biophysics
Volume235
Numero di pubblicazione2
DOI
Stato di pubblicazionePubblicato - dic 1984
Pubblicato esternamente

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