Oxidative Stress-Induced Alterations in PPARγ and Associated Mitochondrial Destabilisation Contribute to Kidney Cell Apoptosis.

Oxidative Stress-Induced Alterations in PPARγ and Associated Mitochondrial Destabilisation Contribute to Kidney Cell Apoptosis. Am J Physiol Renal Physiol. 2014 Aug 13; Authors: Small DM, Morais C, Coombes JS, Bennett NC, Johnson DW, Gobe GC Abstract Mechanism(s) underlying renoprotection by peroxisome proliferator-activated receptor-gamma (PPARγ) agonists in diabetic and non-diabetic kidney disease are not well-understood. Mitochondrial dysfunction and oxidative stress contribute to kidney disease. PPARγ upregulates proteins required for mitochondrial biogenesis. Our aim was to determine whether PPARγ has a role in protecting kidney proximal tubular epithelium (PTE) against mitochondrial destabilisation and oxidative stress. HK-2 PTE cells were subjected to oxidative stress (0.2-1.0mM hydrogen peroxide/H2O2) for 2h and 18h and compared with untreated cells for: apoptosis, mitosis (morphology/biomarkers); cell viability (MTT); superoxide (dihydroethidium/DHE); mitochondrial function (MitoTracker Red; JC-1); ATP (luminescence); and mitochondrial ultrastructure. PPARγ, phospho-PPARγ, PPARγ-coactivator-1α (PGC-1α), Parkin (Park2), p62 and light chain3-beta (LC3β) were investigated using Western blots. PPARγ was modulated using the agonists rosiglitazone, pioglitazone and troglitazone. Mitochondrial destabilisation increased with H2O2 concentration: ATP decreased (2h, 18h; p<0.05); Mitotracker Red and JC-1 fluorescence indi...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research