Cardiac transport of glutathione disulfide and S-conjugate. Studies with isolated perfused rat heart during hydroperoxide metabolism.
The relationship between the intracellular GSSG level and the rate of GSSG release was studied in the isolated perfused heart. GSSG and GSH were released from the heart into the effluent perfusion fluid at rates of 110 and 370 pmol X min-1 X g of heart-1, respectively, much lower than for similar conditions in liver. Perfusion with t-butyl hydroperoxide led to an increase in GSSG release associated with an elevated level of intracellular GSSG. Saturation kinetics was found for the rate of GSSG release with respect to the intracellular GSSG level with an apparent Km value of 30 nmol X g of heart-1 and a maximal rate of 7.5 nmol X min-1 X g of heart-1. The maximal rate of GSSG release was temperature-sensitive with a temperature coefficient of 1.8. When 1-chloro-2,4-dinitrobenzene was infused during perfusion with t-butyl hydroperoxide, mutual competition was found in the release of GSSG and the glutathione-S-conjugate, S-(2,4-dinitrophenyl)-glutathione. The maximal rate for the glutathione-S-conjugate transport was estimated to be 40 nmol X min-1 X g of heart-1. These results are consistent with the existence of a transport system for GSSG in rat heart, its capacity being substantially lower than that for the S-conjugate in heart and that for GSSG in liver. Thus, the sensitivity of heart to oxidative stress may be explained, in part, by a low capacity of GSSG export.
D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D010545:Peroxides; C030190:S-(2,4-dinitrophenyl)glutathione; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D019803:Glutathione Disulfide