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
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Publication date: Available online 12 December 2019Source: Pharmacological ResearchAuthor(s): Jangho Lee, Ju-Yong Hyon, Jin Young Min, Yang Hoon Huh, Hyo Jung Kim, Hayoung Lee, Sung Ho Yun, Chi-Won Choi, Su Jeong Ha, Joon Park, Young-Ho Chung, Hye Gwang Jeong, Sang Keun Ha, Sung Keun Jung, YoonSook Kim, Eun Hee HanAbstractDiabetic nephropathy (DN) is the most common cause of end-stage renal disease in the world. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of DN via multifactorial mechanisms including the generation of oxidative stress and overproduction of various growth factors an...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The objective of this study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between QO2, ATP formation (GATP), ATP hydrolysis (QATP), and Na+ transport in the PT. The present model correctly predicts in vitro and in vivo measurements of QO2, GATP, and ATP and Pi concentrations in PT cells. Our simulations suggest that O2 levels are not rate-limiting in the proximal convoluted tubule absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the GATP/Q...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we aim to understand the molecular mechanism of the protective effect of metformin in NAFLD, focusing on lipotoxicity. Cell death was studied in HepG2 cells and primary rat hepatocytes exposed to palmitate and metformin. Metformin ameliorated palmitate-induced necrosis and apoptosis (decreased caspase-3/7 activity by 52% and 57% respectively) in HepG2 cells. Metformin also reduced palmitate-induced necrosis in primary rat hepatocytes (P 
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
We report that Werner syndrome (WS) is associated with a significant mitochondrial dysfunction, mainly manifested as defective mitophagy. This is reflected in lower NAD+ levels across species from worms to humans. NAD+ supplementation improves mitochondrial function and other age-related metabolic outcomes. Mitochondrial disease can manifest itself in multiple clinical outcomes amongst which neurodegeneration and impaired metabolism are common. Some features of WS may be explained by genomic instability due to mutation in the gene encoding the Werner protein (WRN), an important DNA helicase/exonuclease involved in DNA repa...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Mitochondrial dysfunction is involved in the pathology of two major blinding retinal diseases, diabetic retinopathy (DR) and age-related macular degeneration (AMD). These diseases accumulate mitochondrial defects in distinct retinal subcellular structures, the vascular/neural network in DR and the retinal pigment epithelium (RPE) in AMD. These mitochondrial defects cause a metabolic crisis that drives disease. With no treatments to stop these diseases, coupled with an increasing population suffering from AMD and DR, there is an urgent need to develop new therapeutics targeting the mitochondria to prevent ...
Source: Trends in Molecular Medicine - Category: Molecular Biology Authors: Tags: Trends Mol Med Source Type: research
Protective effects of hydrogen‑rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP‑sensitive potassium channel channels in rats. Mol Med Rep. 2019 Nov 05;: Authors: Jiao Y, Yu Y, Li B, Gu X, Xie K, Wang G, Yu Y Abstract It has previously been demonstrated that hyperglycemia‑induced oxidative stress and inflammation are closely associated with the development of diabetic complications, including diabetic neuropathy. Additionally, mitochondrial ATP‑sensitive potassium (Mito‑K‑ATP) channels play a homeostatic role on blood glucose regulation ...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
AbstractPurpose of ReviewThe goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression.Recent FindingsMitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a pro...
Source: Current Diabetes Reports - Category: Endocrinology Source Type: research
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