A5023426107- Nitric Oxide and Endothelin Effects
- Redox biology and oxidative stress
- Renin-Angiotensin System Studies
- Sulfur Compounds in Biology
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Cardiac electrophysiology and arrhythmias
- Eicosanoids and Hypertension Pharmacology
- Ion channel regulation and function
- Hormonal Regulation and Hypertension
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mitochondrial Function and Pathology
- Free Radicals and Antioxidants
- Phosphodiesterase function and regulation
- Advanced Glycation End Products research
- Biochemical effects in animals
- Ion Transport and Channel Regulation
- Connexins and lens biology
- S100 Proteins and Annexins
- Adipose Tissue and Metabolism
- Melanoma and MAPK Pathways
- Cardiovascular Function and Risk Factors
- Heat shock proteins research
- Alcohol Consumption and Health Effects
- Antioxidant Activity and Oxidative Stress
Queen Mary University of London
2019-2025
William Harvey Research Institute
2019-2025
Universität Hamburg
2022
University Medical Center Hamburg-Eppendorf
2022
Stockton University
2022
University of Washington
2022
United States Air Force Academy
2022
KU Leuven
2022
Western Washington University
2022
Rowan University
2022
Changes in the concentration of oxidants cells can regulate biochemical signaling mechanisms that control cell function. We have found guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG) functions directly as a redox sensor. The Ialpha isoform, PKGIalpha, formed an interprotein disulfide linking its two subunits exposed to exogenous hydrogen peroxide. This oxidation activated vitro, and rat tissues. affinity for substrates it phosphorylates was enhanced by formation....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTACCELERATION OF THE DIELS-ALDER REACTION BY ALUMINUM CHLORIDEPeter Yates and Philip EatonCite this: J. Am. Chem. Soc. 1960, 82, 16, 4436–4437Publication Date (Print):August 1, 1960Publication History Published online1 May 2002Published inissue 1 August 1960https://pubs.acs.org/doi/10.1021/ja01501a085https://doi.org/10.1021/ja01501a085research-articleACS PublicationsRequest reuse permissionsArticle Views4321Altmetric-Citations285LEARN ABOUT THESE...
Objective— Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) a ROS-generating enzyme expressed endothelium, levels which increase pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H 2 O ), but its role vivo remains unclear. Methods and Results— We generated transgenic mice with endothelium-targeted Nox4 overexpression (Tg) to study Nox4. Tg demonstrated...
A principal product of the reaction between a protein cysteinyl thiol and hydrogen peroxide is sulfenic acid. Because acid formation reversible, it provides mechanism whereby changes in cellular concentration may directly control function. We have developed methods for detection purification proteins oxidized this way. The methodology based on arsenite-specific reduction under denaturing conditions their subsequent labeling with biotin–maleimide. Arsenite-dependent signal generation was...
Here we demonstrate that type I protein kinase A is redoxactive, forming an interprotein disulfide bond between its two regulatory RI subunits in response to cellular hydrogen peroxide. This oxidative formation causes a subcellular translocation and activation of the kinase, resulting phosphorylation established substrate proteins. The mediated at least part by oxidized form having enhanced affinity for α-myosin heavy chain, which serves as (PKA) anchor localizes PKA myofilament substrates...
Regulation of protein function by reversible cysteine-targeted oxidation can be achieved multiple mechanisms, such as S-glutathiolation, S-nitrosylation, sulfenic acid, sulfinic and sulfenyl amide formation, well intramolecular disulfide bonding vicinal thiols. Another cysteine state with regulatory potential involves the formation intermolecular disulfides. We utilized two-dimensional sequential non-reducing/reducing SDS-PAGE (diagonal electrophoresis) to investigate in adult cardiac...
The rate of oxidation palmitate-l-C14 to C14O2 by rat skeletal muscle in vitro was shown increase markedly as a function the concentrations free fatty acids (FFA) medium. Neither epinephrine nor glucose had any important effect. incorporation into tissue neutral lipids also increased higher levels FFA At given concentration this but not altered epinephrine. It is concluded that deposition triglyceride reported occur after or norepinephrine administration due effects these hormones on serum...
Dysregulated blood pressure control leading to hypertension is prevalent and a risk factor for several common diseases. Fully understanding regulation offers the possibility of developing rationale therapies alleviate associated disease risks. Although hydrogen sulfide (H2S) well-established endogenous vasodilator, molecular basis its blood-pressure lowering action incompletely understood. H2S-dependent vasodilation in vivo was mediated by it catalyzing formation an activating interprotein...
S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded a ubiquitous, stable post-translational modification that directly regulates many proteins. Such widespread role would appear be incompatible with the inherent lability of S-nitroso bond, especially its propensity rapidly react thiols generate disulfide bonds. As anticipated, we observed robust and protein S-nitrosation after exposing cells nitrosocysteine or lipopolysaccharide. Proteins detected using...
Hypoxic pulmonary vasoconstriction (HPV) optimizes systemic oxygen delivery by matching ventilation to perfusion. HPV is intrinsic artery smooth muscle cells (PASMCs). Hypoxia dilates arteries, including renal arteries. sensed changes in mitochondrial-derived reactive species, notably hydrogen peroxide (H2O2) ([H2O2]mito). Decreases [H2O2]mito elevate vascular tone increasing intracellular calcium ([Ca2+]i) through reduction-oxidation regulation of ion channels. Although mimicked the Complex...
We have developed methods that allow detection, quantitation, purification, and identification of cardiac proteins<i>S</i>-thiolated during ischemia reperfusion. Cysteine was biotinylated loaded into isolated rat hearts. During oxidative stress, biotin-cysteine forms a disulfide bond with reactive protein cysteines, these can be detected by probing Western blots streptavidin-horseradish peroxidase. <i>S</i>-Thiolated proteins were purified using streptavidin-agarose. Thus, we demonstrated...
4-Hydroxy-2-nonenal (HNE) is a major lipid peroxidation product formed during oxidative stress. Because of its reactivity with nucleophilic compounds, particularly metabolites and proteins containing thiol groups, HNE cytotoxic. The aim this study was to assess the extent time course for formation HNE-modified ischemia plus reperfusion in isolated rat hearts. With an antibody HNE-Cys/His/Lys densitometry Western blots, we quantified amount HNE-protein adduct heart. By taking biopsies from...
Glutathione disulfide (GSSG) accumulates in cells under an increased oxidant load, which occurs during neurohormonal or metabolic stimulation as well many disease states. Elevated GSSG promotes protein S-glutathiolation, a reversible post-translational modification, can directly alter regulate function. We developed novel strategies for the study of S-glutathiolation that involved simple synthesis N,N-biotinyl glutathione (biotin-GSSG). Biotin-GSSG treatment mimics defined component...
The mechanism by which the cardiac Na/K ATPase (NKA) is regulated phosphorylation controversial. We have used perforated-patch technique to limit cell dialysis and maintain conditions as near physiological possible.NKA pump current (I(p)) was measured in isolated guinea pig ventricular myocytes, its components (I(alpha 1) I(alpha 2)) defined their differing dihydroouabain sensitivities.Treatment with 1 micromol/l forskolin for 4 min at 35 degrees C caused a significant increase I(alpha1) of...