Search results for "MITOCHONDRION"

Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochon…

2003

IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly…

Mitochondrial dysfunction in cholestatic liver diseases

2011

et al.

PGC-1α: a master gene that is hard to master

2012

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcriptional coactivator that favorably affects mitochondrial function. This concept is supported by an increasing amount of data including studies in PGC-1α gene-deleted mice, suggesting that PGC-1α is a rescue factor capable of boosting cell metabolism and promoting cell survival. However, this view has now been called into question by a recent study showing that adeno-associated virus-mediated PGC-1α overexpression causes overt cell degeneration in dopaminergic neurons. How is this to be understood, and can these seemingly conflicting findings tell us something about the role of PGC-1α in cell stress and in cont…

The HIF1α-PFKFB3 Pathway: A Key Player in Diabetic Retinopathy

2021

Abstract Diabetic retinopathy (DR) is the leading cause of blindness for adults in developed countries. Both microvasculopathy and neurodegeneration are implicated in mechanisms of DR development, with neuronal impairment preceding microvascular abnormalities, which is often underappreciated in the clinic. Most current therapeutic strategies, including anti-vascular endothelial growth factor (anti-VEGF)-antibodies, aim at treating the advanced stages (diabetic macular edema and proliferative diabetic retinopathy) and fail to target the neuronal deterioration. Hence, new therapeutic approach(es) intended to address both vascular and neuronal impairment are urgently needed. The hypoxia-induci…

Expression of R-3-hydroxybutyrate dehydrogenase, a ketone body converting enzyme in heart and liver mitochondria of ruminant and non-ruminant mammals

1992

1. The properties of rat liver and bovine heart R-3-hydroxybutyrate dehydrogenase (BDH) have been extensively studied in the past 20 years, but little is known concerning the biogenesis and the regulation of this dehydrogenase over different species. 2. In addition, controversial results were often reported concerning the activity, the level and the subcellular location of this enzyme in ruminants. 3. BDH activity found in liver and kidney mitochondria from ruminants (cow and sheep) is low, while it is much higher in rat. 4. However, the enzyme activity is detected in microsomes and in cytosol of liver and of kidney cells from ruminants. These activities are not correlated to ketonaemia lev…

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

2019

Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included. Anthropometric and analytical measurements were performed. We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2&alpha

Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance.

2009

Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial function.Our objective was to assess mitochondrial function by evaluating mitochondrial oxygen (O(2)) consumption, reactive oxygen species (ROS) production, levels of glutathione (GSH), the oxidized glutathione/GSH ratio, TNFalpha levels, and membrane potential. Additionally, we have evaluated mitochondrial complex I as a target of the oxidative stress responsible for PCOS in polymorphonuclear cells.This was a prospective controlled study conducted in an academic medical center.The study population consisted of 20 lean reproductive-age women with PCOS and 20 body composition-matched controls.…

A Look into Liver Mitochondrial Dysfunction as a Hallmark in Progression of Brain Energy Crisis and Development of Neurologic Symptoms in Hepatic Enc…

2020

Background: The relationship between liver disease and neuropathology in hepatic encephalopathy is well known, but the genesis of encephalopathy in liver failure is yet to be elucidated. Conceptually, the main cause of hepatic encephalopathy is the accumulation of brain ammonia due to impaired liver detoxification function or occurrence of portosystemic shunt. Yet, as well as taking up toxic ammonia, the liver also produces vital metabolites that ensure normal cerebral function. Given this, for insight into how perturbations in the metabolic capacity of the liver may be related to brain pathology, it is crucial to understand the extent of ammonia-related changes in the hepatic metabolism th…

Mitochondrial complex I impairment in leukocytes from type 2 diabetic patients.

2011

Diabetes is associated with oxidative stress. This study evaluated the rates of oxidative stress and mitochondrial impairment in type 2 diabetes patients. The study population consisted of 182 diabetic patients and 50 body-composition- and age-matched controls. We assessed anthropometric and metabolic parameters and mitochondrial function by evaluating mitochondrial oxygen (O2) consumption, reactive oxygen species (ROS) production, glutathione (GSH) levels, GSH/GSSG ratio, mitochondrial membrane potential, and mitochondrial complex I activity in polymorphonuclear cells from diabetes type 2 patients. We found an increase in waist circumference and augmented serum levels of triglycerides, pro…

2019

Charcot–Marie tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic, and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented…