Cysteine oxidation by the postischemic rat kidney.
Renal levels of glutathione are markedly decreased during periods of renal ischemia due to catabolism to cysteine. We previously demonstrated that cysteine accumulates in the tissue as the thiol during ischemia, and resumption of blood flow causes a transient elevation of cysteine levels in the renal venous effluent and return of tissue cysteine levels to control values. In this study, the oxidation state of renal venous cyst(e)ine was determined. Although cysteine accumulated as the reduced thiol during ischemia, cysteine released into the renal vein upon blood reflow was found to be almost entirely in the disulfide form. To distinguish between oxidation of arterial cysteine and renal cysteine formed from ischemia-induced reduced glutathione (GSH) catabolism, a labeling procedure was developed to label kidney GSH with 35S without significant labeling of arterial plasma cyst(e)ine. With this procedure, the source of oxidized cysteine that appeared in the renal venous plasma after ischemia was identified as resulting from renal GSH catabolism. The data indicate that a rapid oxidative process occurs during the initial period of blood reflow to the postischemic kidney. After 35 min of ischemia, 3 mumol cysteine/g dry wt were released from the kidney and oxidized. Cysteine oxidation is also expected to generate oxygen-centered free radicals. Pretreatment of animals with deferoxamine, a iron chelator, was without effect on the relative amount of venous cysteine in the oxidized form, arguing against a role for free iron in this oxidative process.(ABSTRACT TRUNCATED AT 250 WORDS)
Scaduto
R C
RC
Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Grotyohann
L W
LW
D000818:Animals; D003545:Cysteine / Q000097:blood / Q000378:metabolism*; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D007501:Iron / Q000502:physiology; D007511:Ischemia / Q000097:blood / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation
D007555:Isoxazoles; D007501:Iron; D005978:Glutathione; D003545:Cysteine; C006303:acivicin