Search results for "peroxynitrite"

Role of Reduced Lipoic Acid in the Redox Regulation of Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity

2007

Chronic therapy with nitroglycerin results in a rapid development of nitrate tolerance, which is associated with an increased production of reactive oxygen species. We have recently shown that mitochondria are an important source of nitroglycerin-induced oxidants and that the nitroglycerin-bioactivating mitochondrial aldehyde dehydrogenase is oxidatively inactivated in the setting of tolerance. Here we investigated the effect of various oxidants on aldehyde dehydrogenase activity and its restoration by dihydrolipoic acid. In vivo tolerance in Wistar rats was induced by infusion of nitroglycerin (6.6 microg/kg/min, 4 days). Vascular reactivity was measured by isometric tension studies of iso…

[33] Use of repair endonucleases to assess DNA damage by peroxynitrite

1999

Publisher Summary This chapter discusses the use of repair endonucleases to assess DNA damage by peroxynitrite. Repair endonucleases allow a convenient quantification of various types of oxidative modifications induced by peroxynitrite, both in cultured cells and in cell-free DNA. The high sensitivity of the assays allows highly ectotoxic exposure conditions to be avoided—as well as the generation of secondary DNA modifications—that often become a problem at high levels of damage because primary DNA oxidation products can be orders of magnitude more reactive than the original bases, as demonstrated for the reaction of 8-hydroxyguanine with singlet oxygen. The ratio of the various types of m…

Interplays between nitric oxide and reactive oxygen species in cryptogein signalling

2014

The cellular messenger nitric oxide (NO) has many functions in plants. In this study, we investigated its interplays with Reactive Oxygen Species (ROS) in the defense responses triggered by the elicitin cryptogein produced by the oomycete Phytophthora cryptogea. The production of NO induced by cryptogein in tobacco cell suspensions was partly regulated through a ROS-dependent pathway involving the NADPH oxidase NtRBOHD. In turn, NO down-regulated the level of H2O2 derived from NtRBOHD activity. Both NO and ROS synthesis appeared to be under the control of two redundant isoforms of histone deacetylases of type 2 acting as negative regulators of cell death. Occurrence of an interplay between …

2015

The rationale of the study was two-fold: (i) develop a functional synthetic model of the Cytochrome c oxidase (CcO) active site, (ii) use it as a convenient tool to understand or predict the outcome of the reaction of CcO with ligands (physiologically relevant gases and other ligands). At physiological pH and potential, the model catalyzes the 4-electron reduction of oxygen. This model was immobilized on self-assembled-monolayer (SAM) modified electrode. During catalytic oxygen reduction, electron delivery through SAMs is rate limiting, similar to the situation in CcO. This model contains all three redox-active components in CcO's active site, which are required to minimize the production o…

Uncoupling of Endothelial Nitric Oxide Synthase in Cardiovascular Disease and its Pharmacological Reversal

2010

Publisher Summary This chapter discusses the role of oxidative stress in vascular dysfunction and atherogenesis, and strategies for its prevention. Endothelial dysfunction and oxidative stress have been identified as a common denominator of many cardiovascular risk factors. They support pro-inflammatory, prothrombotic, proliferative, and vasoconstrictor mechanisms that are involved in the initiation, progression, and complications of atherosclerosis. The pathophysiologic causes of oxidative stress involve changes in a number of different enzyme systems. Increased production of ROS by uncoupled eNOS is likely to contribute significantly to vascular oxidative stress and endothelial dysfunctio…

Involvement of Peroxynitrite on the Early Loss of P450 in Short-Term Hepatocyte Cultures

2001

The biological chemistry of nitric oxide (NO) in the oxygenated cellular environment is extremely complex. It involves the direct interaction of NO with specific biomolecules and the so-called indirect effects, due to secondary more potent oxidant species derived from NO which are also able to react with DNA, lipids, thiols and transition metals (Wink et al. 1996; Nathan, 1992). In addition to its regulatory role as a signalling molecule (Nathan, 1992; Moncada and Palmer, 1991) it has become evident that NO (or NO-derived species) is a critical factor involved in various toxicological mechanisms (Wink et al. 1996; Wang et al. 1998; Estevez et al. 1999; Wink et al. 1999). Some controversy ex…

Unique Features of the Low Molecular Weight Probe Salicylaldehyde in the Detection of Nanomolar Peroxynitrite Fluxes

2012

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…

Endothelial nitric oxide synthase in vascular disease: from marvel to menace.

2006

Nitric oxide (NO·) is an important protective molecule in the vasculature, and endothelial NO· synthase (eNOS) is responsible for most of the vascular NO· produced. A functional eNOS oxidizes its substrate l -arginine to l -citrulline and NO·. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate l -arginine, and the essential cofactor (6 R )-5,6,7,8-tetrahydro- l -biopterin (BH 4 ), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinu…

Targeting Heme-Oxidized Soluble Guanylate Cyclase

2007

Increased peripheral vascular resistance is a hallmark of advanced chronic congestive heart failure (CHF) and contributes to the phenomenon of increased afterload that complicates that condition. Multiple factors have been proposed to contribute to this phenomenon, such as increased sodium water content of the vasculature, increased activation of neurohormonal vasoconstrictor forces, and intrinsic abnormalities of the vasculature. During the past decade, it has also been shown that CHF is associated with a severe degree of endothelial dysfunction in experimental animals, as well as in humans. Given that the endothelium, as well as endothelium-dependent vasodilation, plays a crucial role in …