TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in mouse podocytes, mediated in part by the mTOR pathway.

TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in mouse podocytes, mediated in part by the mTOR pathway. Am J Physiol Renal Physiol. 2013 Sep 18; Authors: Abe Y, Sakairi T, Beeson C, Kopp JB Abstract Transforming growth factor (TGF)-β has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-β1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/mL of TGF-β1 for 24, 48, and 72 hours. TGF-β1 (3 ng/mL) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 hours, respectively. ATP content was increased 19% and 30% relative to control after 48 and 72 hours exposure, respectively. Under conditions of maximal mitochondrial function, TGF-β1 increased palmitate-driven OCR by 49%. Thus, TGF-β1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-β1 did not increase cell number or mitochondrial DNA copy number, but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-β1 exposure for 48 hours. TGF-β1 activated the mammalian target of ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research