Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal injury. II. Functional alterations of renal cortical mitochondria isolated after mercuric chloride treatment.
The mitochondrial functional defects occurring in the early stages of nephrotoxic renal injury secondary to mercuric chloride have been characterized. No loss of cellular integrity or major mitochondrial structural alterations occurred within the first 3 h after a subcutaneous injection of 5 mg/kg of HgCl2. At 3 h, levels of Hg2+ in renal cortex and isolated renal cortical mitochondria were 1.87 and 0.72 nmol/mg of protein, respectively. Much evidence suggested that this Hg2+ had reached the mitochondria in situ and not during the isolation process. Mitochondria isolated beginning 1 h after treatment with HgCl2 showed depressed ADP uptake. At 2 h, inhibitions of State 3 and 2,4-dinitrophenol uncoupled respiration were detected. Inhibition of 2,4-dinitrophenol-activated mitochondrial ATPase activity was present when measured on mitochondria isolated at 3 h. These effects were not reversed by 2 mM dithioerythritol, 50 mg/ml of albumin or 5 mM MgCl2. Analysis of the data in the context of information available on the in vitro effects of HgCl2 (Weinberg, J. M., Harding, P. G., and Humes, H. D. (1982) J. Biol. Chem. 257, 60-67) indicated that the mitochondrial functional effects could not be attributed to interaction of the mitochondria with Hg2+ during their isolation. These studies implicate compromised mitochondrial bioenergetic function as one of the earliest intracellular effects of Hg2+ in the production of nephrotoxicity but suggest that the intracellular process involves events in addition to those seen with direct exposure of mitochondria to Hg2+ in vitro.
D000135:Acid Phosphatase / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D002950:Citrate (si)-Synthase / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D008627:Mercuric Chloride; D000244:Adenosine Diphosphate; D002950:Citrate (si)-Synthase; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000251:Adenosine Triphosphatases; D008628:Mercury