Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation.
The effect of chronic in vivo glutathione (GSH) depletion by L-buthionine-[S,R]-sulfoximine (BSO) on intracellular and interorgan GSH regulation was investigated in mice both at rest and after an acute bout of exhaustive swim exercise. BSO treatment for 12 days decreased concentrations of GSH in the liver, kidney, quadriceps muscle, and plasma to 28, 15, 7, and 35%, respectively, compared to GSH-adequate mice. In most tissues, with the exception of the kidney, this decrease was associated with a concomitant decrease of glutathione disulfide (GSSG) such that the GSH/GSSG ratio was maintained. GSH depletion caused adaptive changes in several enzymes related to GSH regulation, such as liver glutathione peroxidase (-25%), kidney gamma-glutamyltranspeptidase (+20%), glutathione disulfide reductase (+131%) and glutathione sulfur-transferase (+53%). There was an apparent down-regulation of muscle gamma-glutamyltranspeptidase (-56%) in the GSH-depleted mice, which contributed to a conservation of plasma GSH. Exhaustive exercise in the GSH-adequate state severely depleted GSH content in the liver (-55%) and kidney (-35%), whereas plasma and muscle GSH levels remained constant. However, exercise in the GSH-depleted state exacerbated GSH deficit in the liver (-57%), kidney (-33%), plasma (-65%), and muscle (-25%) in the absence of adequate reserves of liver GSH. Hepatic lipid peroxidation increased by 220 and 290%, respectively, after exhaustive exercise in the GSH-adequate and -depleted mice. We conclude that GSH homeostasis is essential for the prooxidant-antioxidant balance during prolonged physical exercise.
Leeuwenburgh
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Department of Kinesiology, University of Illinois, Urbana 61801.
Ji
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D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D012146:Rest / Q000502:physiology
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione