Search results for "Mitochondrial ROS"
showing 10 items of 28 documents
The role of mitochondrial reactive oxygen species, NO and H2S in ischaemia/reperfusion injury and cardioprotection
2020
Redox signalling in mitochondria plays an important role in myocardial ischaemia/reperfusion (I/R) injury and in cardioprotection. Reactive oxygen and nitrogen species (ROS/RNS) modify cellular structures and functions by means of covalent changes in proteins including among others S‐nitros(yl)ation by nitric oxide (NO) and its derivatives, and S‐sulphydration by hydrogen sulphide (H2S). Many enzymes are involved in the mitochondrial formation and handling of ROS, NO and H2S under physiological and pathological conditions. In particular, the balance between formation and removal of reactive species is impaired during I/R favouring their accumulation. Therefore, various interventions aimed a…
The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in t…
2018
AbstractThere is growing focus on mitochondrial impairment and cardiovascular diseases (CVD) in type 2 diabetes (T2D), and the development of novel therapeutic strategies in this context. It is unknown whether mitochondrial-targeting antioxidants such as SS-31 protect sufficiently against oxidative damage in diabetes. We aimed to evaluate if SS-31 modulates SIRT1 levels and ameliorates leukocyte-endothelium interactions, oxidative stress and inflammation in T2D patients. Anthropometric and metabolic parameters were studied in 51 T2D patients and 57 controls. Production of mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, glutathione content, leukocyte-endotheliu…
The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated fr…
2016
It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA…
Does Metformin Protect Diabetic Patients from Oxidative Stress and Leukocyte-Endothelium Interactions?
2017
Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert t…
Revisiting the Warburg effect: historical dogma versus current understanding
2020
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a 'selfish' metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1 (HIF-1) overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant p53, mutant phosphatase and tensin homologue (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K-Akt-mTORC1, Ras-Raf-MEK-ERK-cMyc, Jak-Stat3) or deactivated (LKB…
Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase
2016
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (…
Role of p62/SQSTM1 beyond autophagy: a lesson learned from drug-induced toxicity in vitro
2018
Background and Purpose SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Its altered function has been associated with different human pathologies, such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood. Experimental Approach We evaluated the expression of p62 in cultured Hep3B cells and their derived ρ° cells (lacking mitochondria), along with markers of autophagy and mitochondrial dysfunction. The …
Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia…
2008
Background: The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Mitochondrial dysfunction represents a key factor in the progression of non-alcoholic steatohepatitis (NASH) as mitochondria are the main cellular site of fatty acid oxidation, ATP synthesis and reactive oxygen species (ROS) production. Aims: (1) To evaluate the role of the uncoupling protein 2 in controlling mitochondrial proton leak and ROS production in NASH rats and humans; and (2) to assess the acute liver damage induced by ischaemia–reperfusion in rats with NASH. Methods: Mitochondria were extracted from the livers of NASH humans and rats fed a methionine and choline de…
Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic…
2017
Abstract Introduction Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. Materials and methods The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesio…
Does Glycemic Control Modulate the Impairment of NLRP3 Inflammasome Activation in Type 2 Diabetes?
2019
Since mitochondrial dysfunction is associated with NOD-like receptor family protein 3 (NLRP3) activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients [25 with glycated hemoglobin (HbA(1c)) 7% and 36 with HbA(1c) 8%] and 40 healthy controls. Total and mitochondrial reactive oxygen species (ROS) production was enhanced in T2D patients, and mitochondrial ROS was more pronounced in those with poor glycemic control. Levels of gene and protein expression of NLRP3 were decreased in both diabetic groups and mo…