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1.
Frank B. Jensen 《BBA》2009,1787(7):841-862
Nitrite is endogenously produced as an oxidative metabolite of nitric oxide, but it also functions as a NO donor that can be activated by a number of cellular proteins under hypoxic conditions. This article discusses the physiological role of nitrite and nitrite-derived NO in blood flow regulation and cytoprotection from a comparative viewpoint, with focus on mammals and fish. Constitutive nitric oxide synthase activity results in similar plasma nitrite levels in mammals and fish, but nitrite can also be taken up across the gills in freshwater fish, which has implications for nitrite/NO levels and nitrite utilization in hypoxia. The nitrite reductase activity of deoxyhemoglobin is a major mechanism of NO generation from nitrite and may be involved in hypoxic vasodilation. Nitrite is readily transported across the erythrocyte membrane, and the transport is enhanced at low O2 saturation in some species. Also, nitrite preferentially reacts with deoxyhemoglobin rather than oxyhemoglobin at intermediate O2 saturations. The hemoglobin nitrite reductase activity depends on heme O2 affinity and redox potential and shows species differences within mammals and fish. The NO forming capacity is elevated in hypoxia-tolerant species. Nitrite-induced vasodilation is well documented, and many studies support a role of erythrocyte/hemoglobin-derived NO. Vasodilation can, however, also originate from nitrite reduction within the vessel wall, and at present there is no consensus regarding the relative importance of competing mechanisms. Nitrite reduction to NO provides cytoprotection in tissues during ischemia-reperfusion events by inhibiting mitochondrial respiration and limiting reactive oxygen species. It is argued that the study of hypoxia-tolerant lower vertebrates and diving mammals may help evaluate mechanisms and a full understanding of the physiological role of nitrite.  相似文献   

2.
Nitrite-exposed (1 mM) rainbow trout Oncorhynchus mykiss fell into two distinct groups with regard to susceptibility and physiological response. Group 1 accumulated nitrite in plasma to a concentration of 2·9 mM within 24 h and died before 48 h. Group 2 survived for 96–144 h, and the accumulation of nitrite was slower, levelling off at a concentration c. 2·3 mM at 72 h. Methaemoglobin (metHb) formation was faster in group 1 than in group 2, but both groups had a metHb fraction c. 70% before dying. The extracellular electrolyte balance was perturbed significantly only in group 1, where plasma [Cl-] decreased and plasma [K+] increased. Heart rate increased rapidly, more in group 1 than in group 2. The tachycardia occurred before any significant changes in metHb or [K+] had developed, suggesting that it was due to nitrite-induced vasodilation, possibly via nitric oxide generated from nitrite, that was countered by an increased cardiac pumping to re-establish blood pressure. Arterial blood pressure and pulse pressure were accordingly kept reasonably constant. Heart rate variability was significantly depressed in group 1. The ventilation rate was significantly increased after 9 h of nitrite exposure in group 1, while the ventilation in group 2 did not increase significantly before 21 h. The data reveal that nitrite has substantial influence on the cardio-respiratory function in fishes.  相似文献   

3.
Nitrite binds reversibly to the ferriheme proteins metmyoglobin and methemoglobin in aqueous buffer solution at a physiological pH of 7.4. The spectral changes recorded for the formation of metMb(NO2-) differ significantly from those observed for the nitrosylation of metMb, which can be accounted for in terms of the different reaction products. Nitric oxide binding to metMb produces a nitrosyl product with Fe(II)-NO+ character, whereas the reaction with nitrite produces an Fe(III)-NO2- complex. The kinetics of the binding and release of nitrite by metMb and metHb were investigated by stopped-flow techniques at ambient and high pressure. The kinetic traces recorded for the reaction of nitrite with metMb exhibit excellent single-exponential fits, whereas nitrite binding to metHb is characterized by double-exponential kinetics which were assigned to the reactions of the alpha- and beta-chains of metHb with NO2-. The rate constants for the binding of nitrite to metMb and metHb were found to be much smaller than those reported for the binding of NO, such that nitrite impurities will not affect the latter reaction. The activation parameters (deltaH++,deltaS(ne),deltaV++) obtained from the temperature and pressure dependence of the reactions support the operation of a dissociative mechanism for the binding and release of nitrite, similar to that found for the binding and release of NO in metMb.  相似文献   

4.
Nitrite is a breakdown product of nitric oxide that in turn is oxidized to nitrate in cells. In this work, we investigated whether reactive oxidant species might be generated during nitrite metabolism in cultured EA.hy926 endothelial cells. Nitrite was taken up by the cells in a time- and concentration-dependent manner and oxidized to nitrate, which accumulated in cells to concentrations almost 10-fold those of nitrite. Conversion of low millimolar concentrations of nitrite to nitrate was associated with increased oxidant stress in the cells. This manifested as increased oxidation of dihydrofluorescein in tandem with depletion of both GSH and ascorbate. Further, loading cells with ascorbate or treatment with desferrioxamine prevented nitrite-induced dihydrofluorescein oxidation. Nitrite within cells also increased the fluorescence of 4-amino-5-methylamino-2′,7′-difluorofluorescein and inhibited the activity of cellular glyceraldehyde 3-phosphate dehydrogenase, which are markers of intracellular nitrosation reactions. Intracellular ascorbate partially prevented both of these effects of nitrite. Although ascorbate can reduce nitrite to nitric oxide at low pH, in endothelial cells loaded with ascorbate, its predominant effect at high nitrite concentrations is to prevent potentially damaging nitrosation reactions.  相似文献   

5.
May JM  Qu ZC  Li X 《Free radical research》2004,38(6):581-589
Nitrite is a breakdown product of nitric oxide that in turn is oxidized to nitrate in cells. In this work, we investigated whether reactive oxidant species might be generated during nitrite metabolism in cultured EA.hy926 endothelial cells. Nitrite was taken up by the cells in a time- and concentration-dependent manner and oxidized to nitrate, which accumulated in cells to concentrations almost 10-fold those of nitrite. Conversion of low millimolar concentrations of nitrite to nitrate was associated with increased oxidant stress in the cells. This manifested as increased oxidation of dihydrofluorescein in tandem with depletion of both GSH and ascorbate. Further, loading cells with ascorbate or treatment with desferrioxamine prevented nitrite-induced dihydrofluorescein oxidation. Nitrite within cells also increased the fluorescence of 4-amino-5-methylamino-2',7'-difluorofluorescein and inhibited the activity of cellular glyceraldehyde 3-phosphate dehydrogenase, which are markers of intracellular nitrosation reactions. Intracellular ascorbate partially prevented both of these effects of nitrite. Although ascorbate can reduce nitrite to nitric oxide at low pH, in endothelial cells loaded with ascorbate, its predominant effect at high nitrite concentrations is to prevent potentially damaging nitrosation reactions.  相似文献   

6.
Previous studies investigating the calcium-dependency of nitric oxide-facilitated striatal dopamine efflux have produced conflicting results. In the current study, we have investigated the role of extracellular calcium in nitric oxide and potassium chloride-evoked striatal dopamine efflux in vivo using microdialysis. Dialysis probes were implanted in the anterior dorsal striatum of chloral hydrate-anesthetized rats. Intrastriatal infusion (20 min fraction) of the nitric oxide generators sodium nitroprusside (200 μM, 500 μM, or 1 mM) and 3-morpholinosydnonimine (1 mM) increased extracellular dopamine levels. The facilitatory effects of 3-morpholinosydnonimine and potassium chloride on dopamine efflux were attenuated following pretreatment (100 min) and co-infusion of calcium free artificial cerebral spinal fluid containing magnesium chloride. Local potassium chloride infusion (100 mM) administered alone elevated striatal dopamine efflux to a similar degree as potassium chloride (100 mM) delivered 60 min after 3-morpholinosydnonimine infusion. These results demonstrate that like potassium chloride, nitric oxide facilitates striatal dopamine efflux in vivo via a mechanism largely dependent on extracellular calcium. Also, as intrastriatal potassium chloride infusion evoked similar increases in extracellular dopamine levels in controls and subjects receiving pretreatment with the NO-generator 3-morpholinosydnonimine, it is unlikely that the functional integrity of DA nerve terminals is compromised via a neurotoxic disruption of plasma membrane potential following enhanced striatal NO production. © 1999 Elsevier Science Ltd. All rights reserved.  相似文献   

7.
Energy conservation in Nitrobacter   总被引:1,自引:0,他引:1  
Abstract The generation of ATP and NADH in total cells of Nitrobacter was measured under aerobic and anaerobic conditions. NADH synthesis was driven by an ATP independent reaction with nitrite or nitric oxide as electron donors. The rate of NADH formation was about 200 times higher, if nitric oxide instead of nitrite served as electron donor. Approximately 2 mol nitric oxide were needed for reduction of 1 mol NAD+. Nitrite caused an end-product inhibition of the nitric oxide induced NADH synthesis. ATP was synthesized by NADH oxidation with oxygen and nitrate as terminal electron acceptors.  相似文献   

8.
Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the stepwise oxidation of NO and have, for years, been regarded as inactive degradation products. As a result, both anions are routinely used as surrogate markers of NO production, with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady-state concentrations of NO metabolites thought to originate from nitric oxide synthase (NOS)-derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS-/-) demonstrated decreased blood and tissue nitrite, nitrate, and nitroso proteins, which were further reduced by low-nitrite (NOx) diet for 1 week. Nitrite supplementation (50 mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS-/- mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency.  相似文献   

9.
Nitrite reductase activity is a novel function of mammalian mitochondria.   总被引:18,自引:0,他引:18  
A V Kozlov  K Staniek  H Nohl 《FEBS letters》1999,454(1-2):127-130
Nitrite, which is the major stable degradation product of nitric oxide, exists in all tissues capable of nitric oxide synthesis from L-arginine. The present study provides experimental evidence that nitrite in contact with respiring mitochondria accepts reducing equivalents from the ubiquinone cycle of the respiratory chain. Univalent reduction of nitrite was totally inhibited by myxothiazol. We therefore conclude on the involvement of redox cycling that ubisemiquinone is associated with the bc1 complex. Recycling of nitric oxide degradation products via these electron carriers may become a threat to energy-linked respiration since nitric oxide in direct contact with mitochondria was shown to slow the energy-linked respiration down and to trigger a mitochondrial source for superoxide radicals. Until now, the existence of nitrite reductase activity was only demonstrated in plants and bacteria. In addition, the present observation elucidates the existence of a nitric oxide synthase-independent nitric oxide source.  相似文献   

10.
Nitrite anions comprise the largest vascular storage pool of nitric oxide (NO), provided that physiological mechanisms exist to reduce nitrite to NO. We evaluated the vasodilator properties and mechanisms for bioactivation of nitrite in the human forearm. Nitrite infusions of 36 and 0.36 micromol/min into the forearm brachial artery resulted in supra- and near-physiologic intravascular nitrite concentrations, respectively, and increased forearm blood flow before and during exercise, with or without NO synthase inhibition. Nitrite infusions were associated with rapid formation of erythrocyte iron-nitrosylated hemoglobin and, to a lesser extent, S-nitroso-hemoglobin. NO-modified hemoglobin formation was inversely proportional to oxyhemoglobin saturation. Vasodilation of rat aortic rings and formation of both NO gas and NO-modified hemoglobin resulted from the nitrite reductase activity of deoxyhemoglobin and deoxygenated erythrocytes. This finding links tissue hypoxia, hemoglobin allostery and nitrite bioactivation. These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation.  相似文献   

11.
Nitrite has now been proposed to play an important physiological role in signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics.  相似文献   

12.
Nitrite has long been known to be vasoactive when present at large concentrations but it was thought to be inactive under physiological conditions. Surprisingly, we have recently shown that supraphysiological and near physiological concentrations of nitrite cause vasodilation in the human circulation. These effects appeared to result from reduction of nitrite by deoxygenated hemoglobin. Thus, nitrite was proposed to play a role in hypoxic vasodilation. We now discuss these results in the context of nitrite reacting with hemoglobin and effecting vasodilation and present new data modeling the nitric oxide (NO) export from the red blood cell and measurements of soluble guanylate cyclase (sGC) activation. We conclude that NO generated within the interior of the red blood cell is not likely to be effectively exported directly as nitric oxide. Thus, an intermediate species must be formed by the nitrite/deoxyhemoglobin reaction that escapes the red cell and effects vasodilation.  相似文献   

13.
Environmental increase in nitrite impairs the function of several aquatic species, including fishes. Nitrite reacts with hemoglobin yielding the non-functional methemoglobin (metHb), and many physiological disturbances can arise. The physiological mechanisms to cope with nitrite are still unclear in fish. Hematological parameters, the role of NADH-methemoglobin reductase system and the electrolytic balance were studied in the freshwater teleost Brycon cephalus (matrinx?) exposed to 0.2, 0.4 and 0.6 mg/L of nitrite N-NO(2) for 24 and 96 h. Hematocrit, total hemoglobin and the red blood cell (RBC) number decreased. Methemoglobin content increased from 1% to 69% for 24 h of exposure and drastically from 5-6% to 90% for 96 h. The activity of NADH-methemoglobin reductase system displayed a tendency of increase in response to nitrite concentration or time of exposure. In the plasma, nitrite was accumulated to values 30-fold higher than the environmental concentration. The plasma K(+) concentration increased only in fish exposed to NO(2) for 24 h. No changes in plasma protein and Na(+) were observed during nitrite exposure but Cl-presented a punctual increase at 0.2 mg/L N-NO(2)-96 h. The hematological data suggest that nitrite caused functional and hemolytic anemia. Furthermore, the electrolytic balance was relatively undisturbed, and the nitrite clearance in matrinx? is likely depending on other factors than NADH-methemoglobin reductase system.  相似文献   

14.
Nitrite is the highly toxic end product of ammonia oxidation that accumulates in the absence of a nitrite-consuming process and is inhibitory to nitrifying and other bacteria. The effects of nitrite on ammonia oxidation rates and regulation of a common gene set were compared in three ammonia-oxidizing bacteria (AOB) to determine whether responses to this toxic metabolite were uniform. Mid-exponential-phase cells of Nitrosomonas europaea ATCC 19718, Nitrosospira multiformis ATCC 25196, and Nitrosomonas eutropha C-91 were incubated for 6 h in mineral medium supplemented with 0, 10, or 20 mM NaNO(2) . The rates of ammonia oxidation (nitrite production) decreased significantly only in NaNO(2) -supplemented incubations of N. eutropha; no significant effect on the rates was observed for N. europaea or N. multiformis. The levels of norB (nitric oxide reductases), cytL (cytochrome P460), and cytS (cytochrome c'-β) mRNA were unaffected by nitrite in all strains. The levels of nirK (nitrite reductase) mRNA increased only in N. europaea in response to nitrite (10 and 20 mM). Nitrite (20 mM) significantly reduced the mRNA levels of amoA (ammonia monooxygenase) in N. multiformis and norS (nitric oxide reductase) in the two Nitrosomonas spp. Differences in response to nitrite indicated nonuniform adaptive and regulatory strategies of AOB, even between closely related species.  相似文献   

15.
Fish that transport environmental chloride with a gill uptake mechanism (gill epithelial Cl(-)/HCO(3)(-)cotransport exchange system), also transport nitrite into plasma through the same mechanism. Because of the relationship between nitrite uptake and the gill chloride uptake mechanism, nitrite uptake can provide insight regarding the method of chloride uptake for fish. This study was designed to determine if non-teleost fishes concentrate nitrite in their plasma, and to determine if chloride inhibits nitrite uptake in non-teleost fish. To determine if bowfin Amia calva, spotted gar Lepisosteus oculatus, alligator gar Atractosteus spatula, and paddlefish Polyodon spathula concentrate environmental nitrite in their plasma, individuals were exposed to concentrations of 0, 1, 10, or 100 mg/L nitrite-N. After exposure, all species had plasma nitrite-N concentrations greater than environmental levels. To determine if chloride inhibits nitrite uptake for spotted gar, alligator gar, and paddlefish, fish were exposed to 1 mg/L nitrite-N and 20 mg/L chloride as calcium chloride, or to 1 mg/L nitrite-N only. Chloride effectively prevented nitrite from being concentrated in the plasma of all species. It appears that non-teleost fish concentrate nitrite in their plasma via their chloride uptake mechanism and that this is an ancestral characteristic for teleost.  相似文献   

16.
Nitrite is a pivotal component of the marine nitrogen cycle. The fate of nitrite determines the loss or retention of fixed nitrogen, an essential nutrient for all organisms. Loss occurs via anaerobic nitrite reduction to gases during denitrification and anammox, while retention occurs via nitrite oxidation to nitrate. Nitrite oxidation is usually represented in biogeochemical models by one kinetic parameter and one oxygen threshold, below which nitrite oxidation is set to zero. Here we find that the responses of nitrite oxidation to nitrite and oxygen concentrations vary along a redox gradient in a Pacific Ocean oxygen minimum zone, indicating niche differentiation of nitrite-oxidizing assemblages. Notably, we observe the full inhibition of nitrite oxidation by oxygen addition and nitrite oxidation coupled with nitrogen loss in the absence of oxygen consumption in samples collected from anoxic waters. Nitrite-oxidizing bacteria, including novel clades with high relative abundance in anoxic depths, were also detected in the same samples. Mechanisms corresponding to niche differentiation of nitrite-oxidizing bacteria across the redox gradient are considered. Implementing these mechanisms in biogeochemical models has a significant effect on the estimated fixed nitrogen budget.Subject terms: Biogeochemistry, Water microbiology, Microbial ecology  相似文献   

17.
Nitrite inhibited active transport of proline in Escherichia coli but not group translocation of sugar via the phosphoenolpyruvate:phosphotransferase system. These results were consistent with previous results that nitrite inhibits active transport, oxygen uptake, and oxidative phosphorylation in aerobic bacteria. Nitrite also inhibited aldolase (EC 4.1.2.13) from E. coli, Pseudomonas aeruginosa, Streptococcus faecalis, and rabbit muscle. Thus, these various data showed that nitrite has more than one site of attack in the bacterial cell. These data also indicated that nitrite is inhibitory to a wide range of physiological types of bacteria.  相似文献   

18.
Human saliva, which contains nitrite, is normally mixed with gastric juice, which contains ascorbic acid (AA). When saliva was mixed with an acidic buffer in the presence of 0.1 mM AA, rapid nitric oxide formation and oxygen uptake were observed. The oxygen uptake was due to the oxidation of nitric oxide, which was formed by AA-dependent reduction of nitrite under acidic conditions, by molecular oxygen. A salivary component SCN enhanced the nitric oxide formation and oxygen uptake by the AA/nitrite system. The oxygen uptake by the AA/nitrite/SCN system was also observed in an acidic buffer solution. These results suggest that oxygen is normally taken up in the stomach when saliva and gastric juice are mixed.  相似文献   

19.
Nitrite inhibited active transport of proline in Escherichia coli but not group translocation of sugar via the phosphoenolpyruvate:phosphotransferase system. These results were consistent with previous results that nitrite inhibits active transport, oxygen uptake, and oxidative phosphorylation in aerobic bacteria. Nitrite also inhibited aldolase (EC 4.1.2.13) from E. coli, Pseudomonas aeruginosa, Streptococcus faecalis, and rabbit muscle. Thus, these various data showed that nitrite has more than one site of attack in the bacterial cell. These data also indicated that nitrite is inhibitory to a wide range of physiological types of bacteria.  相似文献   

20.
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