Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia–reperfusion damage

Webb, David J.; Bond, Richard A.; McLean, Peter G.; Uppal, Rakesh; Benjamin, Nigel; Ahluwalia, Amrita

doi:10.1073/pnas.0402927101

Cited by 549 publications

(523 citation statements)

References 47 publications

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“…The results presented in this work corroborated [22][23][24][25][26][27][28] the mammalian XO-catalysed nitrite reduction and demonstrated, for the first time, that the prokaryotic D. gigas AOR does catalyse the nitrite reduction to NO in the presence of an electron donor to the enzyme, substrate (aldehyde) or not (dithionite) (Figs. 1, 2, 3).…”

Section: Aor and Xo-catalysed Nitrite Reduction To Nosupporting

confidence: 84%

“…The X-band EPR spectra were acquired as described in ''EPR assays'', with a modulation amplitude of 0.5 mT and a microwave power of 633 lW studied by a few groups [18,19]. This activity was then ''forgotten'' until the late 1990s, when the (patho) physiological importance of the generated NO was realised by the groups of Blake, Harrison, Zweier and others [20][21][22][23][24][25][26][27][28] who restudied the nitrate and nitrite reduction. The detailed molecular mechanism of both reductions, however, remains to be elucidated.…”

Section: Aor and Xo-catalysed Nitrite Reduction To Nomentioning

confidence: 99%

“…In particular, the XO ability to catalyse the nitrate reduction has long been known [17][18][19], but only over the last years did this activity begin to be restudied [20,21]. The subsequent XO-catalysed reduction of nitrite to nitric oxide radical (NO) has also been reported over the last decade [20,[22][23][24][25][26][27][28], but it is not yet generally recognised. Interestingly, the mammalian aldehyde oxidase [29], another member of the XO family, was also recently shown to catalyse the nitrite reduction to NO [28,30].…”

Section: Introductionmentioning

confidence: 99%

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Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Maia

Moura

2010

J Biol Inorg Chem

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Mammalian xanthine oxidase (XO) and Desulfovibrio gigas aldehyde oxidoreductase (AOR) are members of the XO family of mononuclear molybdoenzymes that catalyse the oxidative hydroxylation of a wide range of aldehydes and heterocyclic compounds. Much less known is the XO ability to catalyse the nitrite reduction to nitric oxide radical (NO). To assess the competence of other XO family enzymes to catalyse the nitrite reduction and to shed some light onto the molecular mechanism of this reaction, we characterised the anaerobic XO-and AORcatalysed nitrite reduction. The identification of NO as the reaction product was done with a NO-selective electrode and by electron paramagnetic resonance (EPR) spectroscopy. The steady-state kinetic characterisation corroborated the XO-catalysed nitrite reduction and demonstrated, for the first time, that the prokaryotic AOR does catalyse the nitrite reduction to NO, in the presence of any electron donor to the enzyme, substrate (aldehyde) or not (dithionite). Nitrite binding and reduction was shown by EPR spectroscopy to occur on a reduced molybdenum centre. A molecular mechanism of AOR-and XO-catalysed nitrite reduction is discussed, in which the higher oxidation states of molybdenum seem to be involved in oxygen-atom insertion, whereas the lower oxidation states would favour oxygenatom abstraction. Our results define a new catalytic performance for AOR-the nitrite reduction-and propose a new class of molybdenum-containing nitrite reductases.

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Section: Aor and Xo-catalysed Nitrite Reduction To Nosupporting

confidence: 84%

Section: Aor and Xo-catalysed Nitrite Reduction To Nomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Maia

Moura

2010

J Biol Inorg Chem

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“…Such a mechanism may underlie the cardioprotective effects of diverse agents such as SNO-MPG, NO • donors [16], and nitrite [21,50,[85][86][87]. Mitochondria were treated with GSNO or SNO-MPG at the concentrations given on the x-axis, as detailed in the methods.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

Nadtochiy

Burwell

Brookes

2007

Journal of Molecular and Cellular Cardiology

132

118

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Mitochondrial dysfunction is a key pathologic event in cardiac ischemia-reperfusion (IR) injury, and protection of mitochondrial function is a potential mechanism underlying ischemic preconditioning (IPC). Acknowledging the role of nitric oxide (NO • ) in IPC, it was hypothesized that mitochondrial protein S-nitrosation may be a cardioprotective mechanism. The reagent S-nitroso-2-mercaptopropionyl-glycine (SNO-MPG) was therefore developed to enhance mitochondrial Snitrosation and elicit cardioprotection. Within cardiomyocytes, mitochondrial proteins were effectively S-nitrosated by SNO-MPG. Consistent with the recent discovery of mitochondrial complex I as an S-nitrosation target, SNO-MPG inhibited complex I activity and cardiomyocyte respiration. The latter effect was insensitive to the NO • scavenger c-PTIO, indicating no role for NO • -mediated complex IV inhibition. A cardioprotective role for reversible complex I inhibition has been proposed, and consistent with this SNO-MPG protected cardiomyocytes from simulated IR injury. Further supporting a cardioprotective role for endogenous mitochondrial S-nitrosothiols, patterns of protein S-nitrosation were similar in mitochondria isolated from Langendorff perfused hearts subjected to IPC, and mitochondria or cells treated with SNO-MPG. The functional recovery of perfused hearts from IR injury was also improved under conditions which stabilized endogenous S-nitrosothiols (i.e. dark), or by pre-ischemic administration of SNO-MPG. Mitochondria isolated from SNO-MPG-treated hearts at the end of ischemia exhibited improved Ca 2+ handling and lower ROS generation. Overall these data suggest that mitochondrial S-nitrosation and complex I inhibition constitute a protective signaling pathway that is amenable to pharmacologic augmentation.

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“…Cardioprotective effects of nitrite have recently been demonstrated. Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia-reperfusion [6,7]. The underlying mechanisms by which nitrite is reduced to nitric oxide have not yet been fully defined.…”

Section: Introductionmentioning

confidence: 99%

Nitrite confers protection against myocardial infarction: Role of xanthine oxidoreductase, NADPH oxidase and KATP channels

Baker

et al. 2007

Journal of Molecular and Cellular Cardiology

120

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Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia/ reperfusion. However the optimal dose of nitrite and the mechanisms underlying nitrite-induced cardioprotection are not known. We determined the ability of nitrite and nitrate to confer protection against myocardial infarction in two rat models of ischemia/reperfusion injury and the role of xanthine oxidoreductase, NADPH oxidase, nitric oxide synthase and K ATP channels in mediating nitrite-induced cardioprotection. In vivo and in vitro rat models of myocardial ischemia/reperfusion injury were used to cause infarction. Hearts (n=6/group) were treated with nitrite or nitrate for 15 min prior to 30 min regional ischemia and 180 min reperfusion. Xanthine oxidoreductase activity was measured after 15 min aerobic perfusion and 30 min ischemia. Nitrite reduced myocardial necrosis and decline in ventricular function following ischemia/reperfusion in the intact and isolated rat heart in a dose or concentration-dependent manner with an optimal dose of 4 mg/kg in vivo and concentration of 10 μM in vitro. Nitrate had no effect on protection. Reduction in infarction by nitrite was abolished by inhibition of flavoprotein reductases and the molybdenum site of xanthine oxidoreductase, and was associated with an increase in activity of xanthine dehydrogenase and xanthine oxidase during ischemia. Inhibition of nitric oxide synthase had no effect on nitrite-induced cardioprotection. Inhibition of NADPH oxidase and K ATP channels abolished nitrite-induced cardioprotection. Nitrite but not nitrate protects against infarction by a mechanism involving xanthine oxidoreductase, NADPH oxidase and K ATP channels.

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Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia–reperfusion damage

Cited by 549 publications

References 47 publications

Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

Nitrite confers protection against myocardial infarction: Role of xanthine oxidoreductase, NADPH oxidase and KATP channels

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