title: Activities of enzymes involved in renal cellular glutathione metabolism after uninephrectomy in the rat.
abstract: The renal concentration of GSH increases after a significant reduction in renal mass and compensatory renal growth. To test the hypothesis that this increase is due to induction of GSH synthesis, the activities of gamma-glutamylcysteine synthetase, other GSH-dependent enzymes, and selected enzymes involved in cellular energetics were measured in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from male Sprague-Dawley rats that underwent uninephrectomy and compensatory renal growth or from sham-operated rats. Significant increases in cellular content of protein without increases in intracellular content of DNA, in both PT and DT cells, confirmed that cellular hypertrophy had occurred. gamma-Glutamylcysteine synthetase activity increased significantly in PT cells, but not in DT cells, as a result of compensatory cellular hypertrophy, indicating that the effects of cellular hypertrophy on GSH synthesis occurred exclusively in the proximal tubule. Hypertrophy in PT cells, but not in DT cells, was associated with significant increases in activities of glutathione disulfide reductase, both Mg(2+)-dependent and (Na(+)+K+)-stimulated ATPases, succinate:cytochrome c oxidoreductase, and lactate dehydrogenase. Results from this study demonstrate that compensatory hypertrophy occurs in both PT and DT cells and that effects on GSH metabolism and cellular energetics associated with compensatory hypertrophy are more pronounced in PT cells than in DT cells. The findings also support our hypothesis that GSH synthesis is induced in the proximal tubule during compensatory hypertrophy. The increase in GSH synthesis may be an adaptive response to protect against oxidative stress caused by increases in mitochondrial metabolism.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: L H
authors.initials: LH
authors.lastname: Lash
authors.forename: R K
authors.initials: RK
authors.lastname: Zalups
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004734:Energy Metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D006984:Hypertrophy; D007668:Kidney / Q000201:enzymology* / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D008297:Male; D009392:Nephrectomy; D010088:Oxidoreductases / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione); D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; D004247:DNA; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D017301:Ca(2+) Mg(2+)-ATPase; D005721:Glutamate-Cysteine Ligase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione