Mechanisms of the antioxidant effects of nitric oxide

Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Antioxidants and Redox Signaling (Impact Factor: 7.67). 05/2001; 3(2):203-13. DOI: 10.1089/152308601300185179
Source: PubMed

ABSTRACT The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components under high local concentrations of NO. However, NO can also abate the oxidation chemistry mediated by reactive oxygen species such as H2O2 and O2- that occurs at physiological levels of NO. In addition to the antioxidant chemistry, NO protects against cell death mediated by H2O2, alkylhydroperoxides, and xanthine oxidase. The attenuation of metal/peroxide oxidative chemistry, as well as lipid peroxidation, appears to be the major chemical mechanisms by which NO may limit oxidative injury to mammalian cells. In addition to these chemical and biochemical properties, NO can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. This review will address these aspects of the chemical biology of this multifaceted free radical and explore the beneficial effect of NO against oxidative stress.

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Available from: Martin Feelisch, Aug 15, 2015
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    • "immune response, synaptic transmission and dilation of blood vessels. Also, NO is a signaling molecule for the control of blood pressure, and blood flow [19] and it is an important antioxidant [20]. NO is the predominant mediator of normal vascular function, causing smooth muscle relaxation in response to stimulation by other factors such as ischemia [1], so NO availability is an important diagnostic and prognostic factor. "
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    ABSTRACT: High-altitude dwellers have successfully evolved adaptive regulatory mechanisms to survive in a chronic hypoxic environment. Risk assessment regarding high altitude exposure of patients with coronary heart disease (CHD) is of increasing interest. The aim of our study, therefore, was to investigate the biochemical effect of high altitude on modulation of the adaptive response of endothelial functions in patients with cardiovascular diseases (CVD) including myocardial ischemia (MI) or CHD patients living at high altitude in Saudi Arabia. Subjects: This study included 271 subjects composed of 136 patients (84 men and 52 women) suffering from cardiovascular diseases with age range 40 -68 (mean 54) years, and 135 apparently healthy control subjects (69 men and 66 women) with age range 40 -65 (mean 52.5) years. All individuals selected for this study were divided into four groups: A-68 patients suffering from CVD from the cardiology outpatient clinic of Aseer Central Hospital, Abha city, KSA (2,200 meters above sea level) representing high altitude group. B-68 apparently healthy control volunteer subjects from Abha city, KSA. C-68 patients suffering from CVD from the cardiology outpatient clinic of King Abdulaziz Hospital, Makkah city, representing sea level group. D-67 apparently healthy control volunteer subjects from Makkah city. Methods: Serum biochemical measurements for patients and healthy subjects were performed including: Fasting blood sugar, kidney and liver function tests, plasma lipid profile including: total cholesterol (TC), High density lipoprotein cholesterol (HDLc), Low Density Lipoprotein (LDLc) and triglycerides (TG). In addition, parameters of vascular endothelial functions including: Nitric Oxide (NO) in the form of serum nitrite and nitrate (NO 2 -/NO 3 -) concentrations, serum endothelin-1 (ET-1) and vascular cell adhesion molecule (VCAM-1) were also measured. Results: Measurements confirmed higher levels of ET-1 in high altitude control healthy subjects compared with those at sea level (P < 0.001) and also in high altitude cardiovascular patients compared with those at sea level (P < 0.001). Our results also, showed that there was a significant elevation of serum levels of ET-1 in patients group compared to the healthy control group either at high altitude (P < 0.001) or at sea level (P < 0.001). As regards VCAM-1, our results confirmed higher serum levels of VCAM-1 in high altitude control healthy subjects compared with those at sea level (P = 0.015) and also in high altitude cardiovascular patients compared with those at sea level (P = 0.013). Our results also, showed that, there are was a significant elevation of serum levels of VCAM-1 in patients group compared to the healthy control group either at high altitude (P < 0.001) or at sea level (P < 0.001). Our results confirmed higher levels of nitrite/nitrate in high altitude control healthy subjects compared with those at sea level (P = 0.003) and also in high altitude cardiovascular patients compared with those at sea level (P = 0.01). In conclusion, our data suggest that chronic hypoxia at high altitude may lead to higher circulating concentrations of these important vasoactive compounds (VCAM-1, ET-1 and NO), either as a direct result of hypoxia or as adaptive response to chronic high-altitude exposure. This process could imply a potential role for the measurement of these compounds in the prognostic evaluation of patients with CVD. Future studies with the use of ET receptor antagonists as part of a multidrug regimen are also needed especially for cardiovascular disease patients living at high altitude.
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    • "The role of B1R-mediated iNOS activation is currently under investigation and, although high levels of NO are often thought to promote inflammatory responses, the precise role of NO in sepsis and inflammation is still controversial. For example, both animal and clinical studies have shown that NO production may have both salutary and harmful effects (Gross et al., 1996; Artigas et al., 1998; Sittipunt et al., 2001; Wink et al., 2001; Zhu et al., 2001; Tasaka et al., 2002; McClintock et al., 2007; Brovkovych et al., 2008). "
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    ABSTRACT: Kinins are vasoactive peptides that play important roles in cardiovascular homeostasis, pain and inflammation. After release from their precursor kininogens, kinins or their C-terminal des-Arg metabolites activate two distinct G protein-coupled receptors (GPCR), called B2 (B2R) or B1 (B1R). The B2R is expressed constitutively with a wide tissue distribution. In contrast, the B1R is not expressed under normal conditions but is upregulated by tissue insult or inflammatory mediators. The B2R is considered to mediate many of the acute effects of kinins while the B1R is more responsible for chronic responses in inflammation. Both receptors can couple to Galphai and Galphaq families of G proteins to release mediators such as nitric oxide (NO), arachidonic acid, prostaglandins, leukotrienes and endothelium-derived hyperpolarizing factor and can induce the release of other inflammatory agents. The focus of this review is on the different transduction events that take place upon B2R and B1R activation in human endothelial cells that leads to generation of NO via activation of different NOS isoforms. Importantly, B2R-mediated eNOS activation leads to a transient ( approximately 5min) output of NO in control endothelial cells whereas in cytokine-treated endothelial cells, B1R activation leads to very high and prolonged ( approximately 90min) NO production that is mediated by a novel signal transduction pathway leading to post-translational activation of iNOS.
    Neuropeptides 04/2010; 44(2):145-54. DOI:10.1016/j.npep.2009.12.004 · 2.55 Impact Factor
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    • "Increasing data from the literature demonstrate that nitrite is a bioactive oxidation product of NO able to elicit physiopathological effects both in in vivo and in in vitro systems (Wink et al., 2001; Cosby et al., 2003). We then evaluated whether NO x , mainly nitrites generated by SNP under light exposure, could be involved in the cell death process. "
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    ABSTRACT: Sodium nitroprusside (SNP) is a water-soluble iron nitrosyl complex clinically used as a powerful vasodilator for treatment of hypertension; and, in basic research, it has been used to mainly investigate the cytotoxic effects of nitrosative stress. Although NO is considered a pharmacologically active molecule, not all of the biological effects of SNP are dependent on its NO moiety. To elucidate the molecular executioner(s) responsible for SNP cytotoxicity, this study determines the involvement of oxidative stress in p53 activation and apoptotic induction elicited by SNP in SH-SY5Y neuroblastoma cells. We demonstrate that proapoptotic activity of SNP is independent of NO production, because SNP and its 2-day light-exhausted compound SNP(ex) trigger apoptosis to the same extent. We provide evidence for the occurrence of oxidative stress and oxidative damage during both SNP and SNP(ex) exposure and demonstrate that iron-derived reactive oxygen species (ROS) are the genuine mediators of their cytotoxicity. We show that p53 is equally activated upon both SNP and SNP(ex) treatments. Moreover, as demonstrated by small interfering RNA experiments, we indicate its primary role in the induction of apoptosis, suggesting the ineffectiveness of NO in its engagement. The attenuation of p53 levels, obtained by oxy-radical scavengers, is consistent with the recovery of cell viability and ROS decrease, demonstrate that SNP-mediated p53 activation is an event triggered by ROS and/or ROS-mediated damages. Together, our results suggest that investigations of the physiopathological effects of SNP should consider the role of ROS, other than NO, particularly in some conditions such as apoptotic induction and p53 activation.
    Molecular pharmacology 09/2008; 74(5):1234-45. DOI:10.1124/mol.108.048975 · 4.12 Impact Factor
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