A5063553486- Nitric Oxide and Endothelin Effects
- Redox biology and oxidative stress
- Eicosanoids and Hypertension Pharmacology
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sulfur Compounds in Biology
- Sirtuins and Resveratrol in Medicine
- Inflammatory mediators and NSAID effects
- Renin-Angiotensin System Studies
- Cardiovascular Function and Risk Factors
- Glutathione Transferases and Polymorphisms
- Mass Spectrometry Techniques and Applications
- Cardiovascular Disease and Adiposity
- Advanced Proteomics Techniques and Applications
- Cardiac Ischemia and Reperfusion
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Vitamin C and Antioxidants Research
- Hemoglobin structure and function
- Advanced Glycation End Products research
- Autophagy in Disease and Therapy
- Cardiac electrophysiology and arrhythmias
- Biochemical effects in animals
- Angiogenesis and VEGF in Cancer
Boston University
2014-2023
University School
2010-2020
University of Virginia
2019
University of Yamanashi
2019
University of Vermont
2019
University of Dundee
2019
Boston Medical Center
2007-2017
University Medical Center
2007-2017
Ankara University
2017
University of Glasgow
2017
Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, conjunction with a sevenfold higher expression and activity of NO synthase (eNOS). This shown to be consequence age-associated enhanced superoxide (·O2−) production concomitant quenching the formation peroxynitrite leading nitrotyrosilation mitochondrial manganese dismutase (MnSOD), molecular footprint increased levels, which also age. Thus, vascular appears...
Background— Prostaglandins generated by cyclooxygenase (COX) have been implicated in hyperglycemia-induced endothelial dysfunction. However, the role of individual COX isoenzymes as well molecular mechanisms linking oxidative stress and dysfunction diabetes remains to be clarified. Methods Results— Human aortic cells were exposed normal (5.5 mmol/L) high (22.2 glucose. Glucose selectively increased mRNA protein expression COX-2. Its upregulation was associated with an increase thromboxane A...
Enhanced production of reactive oxygen species (ROS) has been recognized as the major determinant age-related endothelial dysfunction. The p66shc protein controls cellular responses to oxidative stress. Mice lacking (p66shc-/-) have increased resistance ROS and a 30% prolonged life span. present study investigates age-dependent changes function in this model.Aortic rings from young old p66shc-/- or wild-type (WT) mice were suspended for isometric tension recording. Nitric oxide (NO) release...
Increased production of reactive oxygen species (ROS) and loss endothelial NO bioavailability are key features vascular disease in diabetes mellitus. The p66(Shc) adaptor protein controls cellular responses to oxidative stress. Mice lacking (p66(Shc-/-)) have increased resistance ROS prolonged life span. present work was designed investigate hyperglycemia-associated changes function a model insulin-dependent mellitus p66(Shc-/-) mouse. wild-type (WT) mice were injected with citrate buffer...
Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function is associated with oxidative gene regulation modification. Vascular aging progressive deterioration of homeostasis leading to reduced relaxation, hypertrophy, higher risk thrombotic events. These effects can be explained by reduction in free bioavailable nitric oxide that inactivated an age-dependent increase superoxide formation. In the present study, mitochondria as source reactive...
Mitochondrial aldehyde dehydrogenase (ALDH-2) was recently identified to be essential for the bioactivation of glyceryl trinitrate (GTN). Here we assessed whether other organic nitrates are bioactivated by a similar mechanism. The ALDH-2 inhibitor benomyl reduced vasodilator potency, but not efficacy, GTN, pentaerythritol tetranitrate (PETN), and in phenylephrine-constricted rat aorta, whereas responses isosorbide dinitrate, isosorbide-5-mononitrate, mononitrate, endothelium-dependent...
Delivering and expressing a gene of interest in cells or living animals has become pivotal technique biomedical research therapy. Among viral delivery systems, adeno-associated viruses (AAVs) are relatively safe demonstrate high transfer efficiency, low immunogenicity, stable long-term expression, selective tissue tropism. Combined with modern technologies, such as cell-specific promoters, the Cre/lox system, genome editing, AAVs represent practical, rapid, economical alternative to...
Recently, we demonstrated that gene ablation of mitochondrial manganese superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age-related vascular dysfunction oxidative stress. The present study has sought investigate the extent oxidant formation in glutathione peroxidase-1–deficient ( GPx-1 −/− ) mice during aging process with special emphasis on dysregulation (uncoupling) endothelial NO synthase. a C57 black 6 (C57BL/6) background at 2, 6, 12 months age were used....
Peroxiredoxin 2 (Prx2) is a thiol protein that functions as an antioxidant, regulator of cellular peroxide concentrations, and sensor redox signals. Its cycle widely accepted to involve oxidation by reduction thioredoxin/thioredoxin reductase. Interactions Prx2 with other thiols are not well characterized. Here we show the active site Cys residues form stable mixed disulfides glutathione (GSH). Glutathionylation was reversed glutaredoxin 1 (Grx1), GSH plus Grx1 able support peroxidase...
Background Mitochondrial reactive oxygen species ( ROS ) are associated with metabolic heart disease MHD ). However, the mechanism by which cause is unknown. We tested hypothesis that mitochondrial a key mediator of . Methods and Results Mice fed high‐fat high‐sucrose HFHS diet develop cardiac diastolic dysfunction oxidative posttranslational modifications proteins. Transgenic mice express catalase in mitochondria wild‐type were an or control for 4 months. Cardiac from ‐fed had 3‐fold...
Significance Many oxidative stimuli engage the 66-kDa Src homology 2 domain-containing protein (p66Shc) to induce reactive oxygen species (ROS). ROS regulated by p66Shc promotes aging and contributes cancer, diabetes, obesity, cardiomyopathy, atherosclerosis. Here we identify a fundamental mechanism that controls p66Shc-regulated ROS. We show is lysine acetylated when cells are faced with an stimulus (diabetes), acetylation of obligatory for p66Shc-induced In addition, lysine-acetylated...
Highlights•High energy phosphates were measured in the hearts of mice with metabolic heart disease (MHD).•The rate myocardial ATP synthesis was decreased MHD.•The free hydrolysis energetic changes MHD are associated pump dysfunction.•The pattern differs qualitatively from dilated cardiomyopathy.AbstractMetabolic syndrome is a cluster obesity-related abnormalities that lead to (MHD) left ventricular dysfunction. Although thought be deficiency, two key questions have not been answered. First,...
Chronic therapy with nitroglycerin results in a rapid development of nitrate tolerance, which is associated an increased production reactive oxygen species. We have recently shown that mitochondria are important source nitroglycerin-induced oxidants and the nitroglycerin-bioactivating mitochondrial aldehyde dehydrogenase oxidatively inactivated setting tolerance. Here we investigated effect various on activity its restoration by dihydrolipoic acid. In vivo tolerance Wistar rats was induced...
Treatment of bovine aortic microsomes containing active prostacyclin synthase (PGI2 synthase) with increasing concentrations peroxynitrite (PN) up to 250 μm PN yielded specific staining this enzyme on Western blots antibodies against 3-nitrotyrosine (3-NT), whereas above 500 additional proteins was also observed. Following treatment 25 PN, PGI2 about half-maximally nitrated and half-inhibited. It then isolated by gel electrophoresis subjected proteolytic digestion several proteases....
Sirtuin-1 (SIRT1) is an NAD(+)-dependent protein deacetylase that sensitive to oxidative signals. Our purpose was determine whether SIRT1 activity the low molecular weight nitrosothiol, S-nitrosoglutathione (GSNO), which can transduce signals into physiological responses. formed mixed disulfides with GSNO-Sepharose, and mass spectrometry identified several cysteines are modified by GSNO, including Cys-67 S-glutathiolated. GSNO had no effect on basal activity, but inhibited stimulation of...
Reactive oxygen species (ROS) are increased in ischemic tissues and necessary for revascularization; however, the mechanism remains unclear. Exposure of cysteine residues to ROS presence glutathione (GSH) generates GSH-protein adducts that specifically reversed by cytosolic thioltransferase, glutaredoxin-1 (Glrx). Here, we show a key angiogenic transcriptional factor hypoxia-inducible (HIF)-1α is stabilized GSH adducts, genetic deletion Glrx improves revascularization. In mouse muscle C2C12...
Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed high-fat, high-sucrose (HFHS) diet, serving as model of human metabolic syndrome, and it is associated with activation proinflammatory oxidant pathways vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) an NAD + -dependent deacetylase regulated by the cellular status. Our goal was to study effects VSM SirT1 on arterial stiffness context diet-induced syndrome. Overnight fasting acutely decreased...