Functional and toxicological characteristics of isolated renal mitochondria: impact of compensatory renal growth.
Mitochondria were isolated from renal cortical homogenates from control rats and rats that had undergone uninephrectomy and compensatory renal growth (NPX rats). Activities of selected mitochondrial processes, including key enzymes of intermediary metabolism, glutathione-dependent enzymes, and glutathione transport, were measured, and the effects of three mitochondrial toxicants were assessed to test the hypothesis that compensatory renal growth is accompanied by increases in mitochondrial metabolism and that this is associated with increased susceptibility to injury from oxidants or other mitochondrial toxicants. Activities of malic and succinic dehydrogenases were significantly higher in mitochondria from NPX rats than in mitochondria from control rats. Although the rates of state 3 respiration were significantly higher in mitochondria from NPX rats, the rates of state 4 respiration and respiratory control ratios were not different between mitochondria from control and NPX rats. Activities of glutathione redox cycle enzymes did not differ significantly between mitochondria from control and NPX rats. However, the rates of uptake of glutathione into mitochondria were approximately 2.5-fold higher in tissue from NPX rats than in tissue from control rats. Incubation of mitochondria from NPX rats with three mitochondrial toxicants [tert-butyl hydroperoxide, methyl vinyl ketone, and S-(1,2-dichlorovinyl)-L-cysteine] caused greater inhibition of state 3 respiration and larger increases in malondialdehyde formation than similar incubations of mitochondria from control rats. These results indicate that mitochondria from hypertrophied renal cells are more sensitive to oxidants or mitochondrial toxicants. Baseline levels of malondialdehyde were also significantly higher in mitochondria from NPX rats, suggesting that a basal oxidant stress exists in mitochondria from hypertrophied cells.
Lash
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LH
Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Ave., Detroit, MI 48201, USA. l.l.lash@wayne.edu
Putt
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DA
Horky
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SJ
Zalups
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D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D005978:Glutathione / Q000378:metabolism; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009392:Nephrectomy; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D000477:Alkylating Agents; D016877:Oxidants; D005978:Glutathione