Premium
MITOCHONDRIAL FUNCTION IN RAT RENAL CORTEX IN RESPONSE TO PROTEINURIA AND IRON
Author(s) -
Harris David CH,
Tay YuetChing
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb02719.x
Subject(s) - endocrinology , medicine , chemistry , mitochondrion , nephrosis , cytochrome c oxidase , respiration , reabsorption , renal function , renal cortex , kidney , biology , biochemistry , anatomy
SUMMARY 1. Proximal tubular cell dysfunction in chronic glomerular disease (CGD) has been ascribed, in part, to reabsorption of transferrin‐iron from tubular fluid and subsequent cytosolic peroxidative injury. To investigate a possible role for altered mitochondrial function in tubular cell injury in CGD, renal cortical mitochondrial respiratory function was examined in rats with adriamycin nephrosis. 2. State 4 (resting) respiration was increased in adriamycin nephrosis in comparison with control (51±2 vs 43±2ng atoms oxygen (0)/min per mg protein, respectively; P < 0.02). 3. Mitochondrial iron concentration was increased in nephrotic rats compared with contro. (9.52±0.70 vs 5.97±0.26 nmol Fe/mg protein, respectively; P < 0.001) and rates of state 3, state 4 and uncoupled respiration and the severity of proteinuria correlated with mitochondrial iron concentration. 4. To further define the relationship between mitochondrial iron accumulation and altered respiratory function, rats were loaded wit. iron. 5. In comparison with control, acute iron loading of normal rats impaired creatinine clearanc. (1.48±0.02 vs 0.40±0.29 mL/min), increased kidney weight (1.33±0.07 vs 1.74±0.14g) and impaired mitochondrial enzyme activity (e.g. cytochrome oxidase 185.0±46.6 vs 362.0±32.8Alog [cytochrome C]/min per mg protein; P < 0.05), but had no significant effect on rates of mitochondrial respiration or on mitochondrial fragility. 6. Mitochondrial iron concentration was not increased by iron loading, despite a similar increment in cytoplasmic iron to that seen in rats with adriamyci. nephrosis. 7. In summary, resting mitochondrial respiration is increased in nephrotic rats in proportion to mitochondrial iron accumulation. Changes in mitochondrial oxygen consumption do not appear to be a primary event in the tubular cell injury of iron loading.