Functional and toxicological characteristics of isolated renal mitochondria: Impact of compensatory renal growth

Citation
Lh. Lash et al., Functional and toxicological characteristics of isolated renal mitochondria: Impact of compensatory renal growth, BIOCH PHARM, 62(3), 2001, pp. 383-395
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
3
Year of publication
2001
Pages
383 - 395
Database
ISI
SICI code
0006-2952(20010801)62:3<383:FATCOI>2.0.ZU;2-1
Abstract
Mitochondria were isolated from renal cortical homogenates from control rat s and rats that had undergone uninephrectomy and compensatory renal growth (NPX rats). Activities of selected mitochondrial processes, including key e nzymes of intermediary metabolism, glutathione-dependent enzymes, and gluta thione transport, were measured, and the effects of three mitochondrial tox icants were assessed to test the hypothesis that compensatory renal growth is accompanied by increases in mitochondrial metabolism and that this is as sociated with increased susceptibility to injury from oxidants or other mit ochondrial toxicants. Activities of malic and succinic dehydrogenases were significantly higher in mitochondria from NPX rats than in mitochondria fro m control rats. Although the rates of state 3 respiration were significantl y higher in mitochondria from NPX rats, the rates of state 4 respiration an d respiratory control ratios were not different between mitochondria from c ontrol and NPX rats. Activities of glutathione redox cycle enzymes did not differ significantly between mitochondria from control and NPX rats. Howeve r, 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. I ncubation 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 inc reases in malondialdehyde formation than similar incubations of mitochondri a from control rats. These results indicate that mitochondria from hypertro phied renal cells are more sensitive to oxidants or mitochondrial toxicants . Baseline levels of malondialdehyde were also significantly higher in mito chondria from NPX rats, suggesting that a basal oxidant stress exists in mi tochondria from hypertrophied cells. (C) 2001 Elsevier Science Inc. All rig hts reserved.