Dysfunction of the PGC-1α/mitochondria axis confers adriamycin-induced podocytes injury.

Dysfunction of the PGC-1α/mitochondria axis confers adriamycin-induced podocytes injury. Am J Physiol Renal Physiol. 2014 May 7; Authors: Zhu C, Xuan X, Che R, Ding G, Zhao M, Bai M, Jia Z, Huang S, Zhang A Abstract Adriamycin (ADR)-induced nephropathy in animals is an experimental analogue of human focal segmental glomerulosclerosis (FSGS), which presents as severe podocyte injury and massive proteinuria and has a poorly understood mechanism. The current study was designed to test the hypothesis that the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/mitochondria axis is involved in ADR-induced podocyte injury. Using MPC5 immortalized mouse podocytes, the ADR dose-dependently induced the downregulation of nephrin and podocin, cell apoptosis, and mitochondrial dysfunction based on the increase in mitochondrial reactive oxygen species (ROS) production, a decrease in mitochondrial DNA (mtDNA) copy number, and the reduction of mitochondrial membrane potential (MMP) and ATP content. Moreover, ADR treatment also remarkably reduced the expression of PGC-1α, an important regulator of mitochondrial biogenesis and function, in podocytes. Strikingly, PGC-1α overexpression markedly attenuated mitochondrial dysfunction, reduction of nephrin and podocin, and the apoptotic response in podocytes following ADR treatment. Moreover, the downregulation of PGC-1α and mitochondria disruption in podocytes were also observed in...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research