Selective inhibition of PKR improves vascular inflammation and remodelling in high fructose treated primary vascular smooth muscle cells

ConclusionIn conclusion PKR activation plays an important role in the pathogenesis of vascular inflammation and remodelling, and therapeutically targeting PKR could be an effective approach to treat the abnormalities associated with vascular complications.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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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
In this study, we reveal that saxagliptin, one of the most widely used DPP-4 inhibitors, exhibits vascular protective effects against oxygen and glucose depletion/reoxygenation (OGD/R) in human brain vascular endothelial cells. Our data show that DPP-4 is fairly expressed in brain endothelial cells and its expression is induced by OGD/R. The results of MTT assay show that inhibition of DPP-4 by saxagliptin ameliorates OGD/R-induced reduced cell viability, and LDH assay demonstrated that saxagliptin reduces cellular toxicity. Furthermore, we show that saxagliptin mitigates OGD/R-induced collapse of mitochondrial membrane po...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Abstract Metabolic diseases, such as type 2 diabetes or obesity, are the consequence of the disruption of the organism's metabolic pathways. The discovery of small non-coding RNAs-microRNAs (miRNAs)-as post-transcriptional gene regulators opened new doors for the development of novel strategies to combat said diseases. The two strands of miR-378a, miR-378a-3p, and miR-378a-5p are encoded in the Ppargc1b gene and have an active role in the regulation of several metabolic pathways such as mitochondrial metabolism and autophagy. Recent studies recognized miR-378a as an important regulator of energy and glucose homeos...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
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