Search results for "Prostacyclin synthase"
showing 7 items of 7 documents
Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
2017
Abstract Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone‐mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose‐dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase‐2 (COX‐2) and prostac…
Mitochondrial aldehyde dehydrogenase (ALDH-2)--maker of and marker for nitrate tolerance in response to nitroglycerin treatment.
2008
The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Long-term nitrate treatment also is associated with decreased vascular responsiveness caused by changes in intrinsic mechanisms of the tolerant vasculature itself. According to the oxidative stress concept, increased vascular superoxide and peroxynitrite production as well as an increased sensitivity to vasoconstrictors secondary to activation of protein kinase C as well as vascular NADPH oxidases contribute to the development of tolerance. Recent experimental work has defined new tolerance mechanisms, including inhibition of the enzyme that bioactivates …
Increased Circulating Levels of 3-Nitrotyrosine Autoantibodies
2012
3-nitrotyrosine formation is an oxidative protein modification that was first discovered in vivo in the early 1990s by Beckman and colleagues.1,2 The biological relevance of this process was extensively investigated in the subsequent years and further facilitated by the development of 3-nitrotyrosine–specific antibodies.3 Protein tyrosine nitration is mainly mediated by 3 biochemical processes (Figure): (1) by peroxynitrite (ONOO−) formation,4–6 the reaction product of nitric oxide (•NO) and superoxide (•O2−); (2) by a (myelo)peroxidase-catalyzed nitrogen dioxide radical (•NO2) formation from hydrogen peroxide and nitrite;7,8 and (3) by a nonspecific formation of the nitrogen dioxide radica…
Characterization of monoclonal antibodies generated against bovine and porcine prostacyclin synthase and quantitation of bovine prostacyclin synthase
1994
AbstractMonoclonal antibodies were raised against prostacyclin synthases purified from bovine and porcine aortae, respectively. Two monoclonal antibodies, RS1 and RS2, were purified and characterized. As shown by enzyme activity precipitation and Western blot analysis, in solubilized bovine and porcine aortae microsomes the monoclonal antibodies reacted only with prostacyclin synthase. The monoclonal antibody RS1 cross-reacts with partially purified prostacyclin synthase from human umbilical veins in an ELISA-based assay. None of the antibodies inhibited the enzyme activity. By combination of the monoclonal antibody RS2 with a polyclonal antibody we established an enzyme-linked immunosorben…
Explaining the phenomenon of nitrate tolerance.
2005
During the last century, nitroglycerin has been the most commonly used antiischemic and antianginal agent. Unfortunately, after continuous application, its therapeutic efficacy rapidly vanishes. Neurohormonal activation of vasoconstrictor signals and intravascular volume expansion constitute early counter-regulatory responses (pseudotolerance), whereas long-term treatment induces intrinsic vascular changes, eg, a loss of nitrovasodilator-responsiveness (vascular tolerance). This is caused by increased vascular superoxide production and a supersensitivity to vasoconstrictors secondary to a tonic activation of protein kinase C. NADPH oxidase(s) and uncoupled endothelial nitric oxide synthase …
Progestogens reduce thromboxane production by cultured human endothelial cells.
2011
Objectives Progestogens have been poorly studied concerning their roles in endothelial physiology. Prostanoids are vasoactive compounds, such as thromboxane A2, a potent vasoconstrictor, and prostacyclin, a vasodilator. We examined the effects of two progestogens used clinically, progesterone and medroxyprogesterone acetate, on thromboxane A2 production by cultured human umbilical vein endothelial cells (HUVEC) and investigated the role of progesterone receptors and the enzymes involved in production of thromboxane A2 and prostacyclin. Methods Cells were exposed to 1‐100 nmol/l of either progesterone or medroxyprogesterone acetate, and thromboxane A2 production was measured in culture mediu…
Protein tyrosine nitration and thiol oxidation by peroxynitrite-strategies to prevent these oxidative modifications.
2013
The reaction product of nitric oxide and superoxide, peroxynitrite, is a potent biological oxidant. The most important oxidative protein modifications described for peroxynitrite are cysteine-thiol oxidation and tyrosine nitration. We have previously demonstrated that intrinsic heme-thiolate (P450)-dependent enzymatic catalysis increases the nitration of tyrosine 430 in prostacyclin synthase and results in loss of activity which contributes to endothelial dysfunction. We here report the sensitive peroxynitrite-dependent nitration of an over-expressed and partially purified human prostacyclin synthase (3.3 μM) with an EC50 value of 5 μM. Microsomal thiols in these preparations effectively co…