Search results for "ADP"
showing 10 items of 423 documents
Glucose 6-P dehydrogenase delays the onset of frailty by protecting against muscle damage.
2021
Background: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. Methods: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigate…
Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal
2006
Endothelial NO synthase (eNOS) is the predominant enzyme responsible for vascular NO synthesis. A functional eNOS transfers electrons from NADPH to its heme center, where L-arginine is oxidized to L-citrulline and NO. Common conditions predisposing to atherosclerosis, such as hypertension, hypercholesterolemia, diabetes mellitus and smoking, are associated with enhanced production of reactive oxygen species (ROS) and reduced amounts of bioactive NO in the vessel wall. NADPH oxidases represent major sources of ROS in cardiovascular pathophysiology. NADPH oxidase-derived superoxide avidly interacts with eNOS-derived NO to form peroxynitrite (ONOO(-)), which oxidizes the essential NOS cofactor…
Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?
2015
Physical exercise increases the cellular production of reactive oxygen species (ROS) in muscle, liver, and other organs. This is unlikely due to increased mitochondrial production but rather to extramitochondrial sources such as NADPH oxidase or xanthine oxidase. We have reported a xanthine oxidase-mediated increase in ROS production in many experimental models from isolated cells to humans. Originally, ROS were considered as detrimental and thus as a likely cause of cell damage associated with exhaustion. In the past decade, evidence showing that ROS act as signals has been gathered and thus the idea that antioxidant supplementation in exercise is always recommendable has proved incorrect.…
Oxidative stress in vascular disease and its pharmacological prevention
2013
Cardiovascular risk factors lead to enhanced production of reactive oxygen species (ROS) generated by NADPH oxidase, xanthine oxidase (XO), the mitochondrial electron-transport chain (ETC), and dysfunctional endothelial nitric oxide synthase (eNOS). When the capacity of antioxidant defense systems [e.g., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), heme oxygenase (HO), paraoxonase (PON)] is exceeded, this results in oxidative stress, which can promote atherogenesis. Therefore, pharmacological means to prevent oxidative stress are of major therapeutic interest. Some established drugs and novel therapeutic approaches can prevent oxidative stress and, presumably, vascula…
Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells
2007
The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and …
Pathophysiology of polymorphonuclear leukocyte in arterial hypertension
2009
This review shows how polymorphonuclear leukocytes (PMNs) play a pivotal role in the development of the organ injury that is associated with arterial hypertension. Elevated white blood cell count and higher levels of PMNs activation are risk factors for arterial hypertension and cardiovascular disease. Spontaneously activated PMNs release proinflammatory factors and reactive oxygen species, which have negative effects on vascular tone and on their adhesion to the endothelium. The oxidative stress in hypertensive PMNs is revealed by increased NADPH-oxidase production and lipid peroxidation and by decreased cytosolic and mitochondrial superoxide dismutase concentrations. The overexpression of…
Sirolimus-Induced Vascular Dysfunction
2008
Objectives This study sought to analyze mechanisms that mediate vascular dysfunction induced by sirolimus. Background Despite excellent antirestenotic capacity, sirolimus-eluting stents have been found to trigger coronary endothelial dysfunction and impaired re-endothelialization. Methods To mimic the continuous sirolimus exposure of a stented vessel, Wistar rats underwent drug infusion with an osmotic pump for 7 days. Results Sirolimus treatment caused a marked degree of endothelial dysfunction as well as a desensitization of the vasculature to the endothelium-independent vasodilator nitroglycerin. Also, sirolimus stimulated intense transmural superoxide formation as detected by dihydroeth…
Characterization of nitric oxide synthase isoforms expressed in different structures of the guinea pig cochlea.
1997
Nitric oxide synthase (NOS) activity and NADPH diaphorase staining has previously been reported in mammalian cochlea. Here we demonstrate immunoreactivity for neuronal-type NOS I and endothelial-type NOS III in the cochlea of the guinea pig. NOS I immunoreactivity was seen in inner and outer hair cells, and spiral ganglion cells. Staining for NOS I was also shown in basal and intermediate cells of the stria vascularis, spiral ligament cells, and the media of vessels near the modiolus. An antibody to NOS III stained primarily vascular endothelial cells. Some NOS III immunoreactivity was also detected in spiral ganglion cells. An antibody to the inducible-type NOS II did not stain any structu…
Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes
1996
Mitochondrial damage may be a major cause of cellular aging. So far, this hypothesis had only been tested using isolated mitochondria. The aim of this study was to investigate the involvement of mitochondria in aging using whole liver cells and not isolated mitochondria only. Using flow cytometry, we found that age is associated with a decrease in mitochondrial membrane potential (30%), an increase in mitochondrial size, and an increase in mitochondrial peroxide generation (23%). Intracellular peroxide levels were also increased. The number of mitochondria per cell and inner mitochondrial membrane mass did not change. Gluconeogenesis from glycerol or fructose (mitochondrial-independent) did…
Genetic variants in the MTHFR are not associated with fatty liver disease.
2020
The common missense sequence variants of methylenetetrahydrofolate reductase (MTHFR), rs1801131 (c.A1298C) and rs1801133 (c.C677T), favour the development of hyperhomocysteinemia and diminished DNA methylation. Previous studies, carried out in small series and with suboptimal characterization of the hepatic phenotype, tested the association of these genetic variants with fatty liver disease (FLD), with conflicting results. Here, we assessed the association of rs1801131 and rs1801133 with hepatic phenotype in the Liver Biopsy Cross-Sectional Cohort, a large cohort (n=1375 from Italy and 411 from Finland) of European individuals with suspect FLD associated with dysmetabolism. A total of 1786 …