Deletion of Protein Kinase C- ε Attenuates Mitochondrial Dysfunction and Ameliorates Ischemic Renal Injury.

This study tested whether deletion of the PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44% and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT, but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO, but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced decreases in: 1) complex I- and complex II-coupled state 3 respirations, and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates: 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3)...

Source: Am J Physiol Renal P... - October 18, 2016 Category: Urology & Nephrology Authors: Nowak G, Takacsova Bakajsova D, Megyesi J Tags: Am J Physiol Renal Physiol Source Type: research