Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells.

We previously reported that mitochondrial function, intracellular ATP levels, and complex I activity are decreased in renal proximal tubular cells (RPTC) after oxidant (tert-butyl hydroperoxide; TBHP)-induced injury. This study examined the hypothesis that succinate supplementation decreases mitochondrial dysfunction, ameliorates energy deficits, and increases viability in TBHP-injured RPTC. Basal and uncoupled respirations in injured RPTC decreased 33 and 35%, respectively, but remained unchanged in injured RPTC supplemented with 10 mM succinate (electron donor to respiratory complex II).

Activation of ERK1/2 pathway mediates oxidant-induced decreases in mitochondrial function in renal cells.

Previously, we showed that oxidant exposure in renal proximal tubular cells (RPTC) induces mitochondrial dysfunction mediated by PKC-epsilon. This study examined the role of ERK1/2 in mitochondrial dysfunction induced by oxidant injury and whether PKC-epsilon mediates its effects on mitochondrial function through the Raf-MEK1/2-ERK1/2 pathway. Sublethal injury produced by tert-butylhydroperoxide (TBHP) resulted in three- to fivefold increase in phosphorylation of ERK1/2 and p38 but not JNK.

Protein kinase C-epsilon modulates mitochondrial function and active Na+ transport after oxidant injury in renal cells.

The aim of this study was to determine whether protein kinase C-epsilon (PKC-epsilon) is involved in the repair of mitochondrial function and/or active Na+ transport after oxidant injury in renal proximal tubular cells (RPTC). Sublethal injury was produced in primary cultures of RPTC using tert-butylhydroperoxide (TBHP), and the recovery of functions was examined. PKC-epsilon was activated three- to fivefold after injury.