Role for the Salmonella Flavohemoglobin in Protection from Nitric Oxide

Crawford, Michael J.; Goldberg, Daniel E.

doi:10.1074/jbc.273.20.12543

Cited by 164 publications

(156 citation statements)

References 46 publications

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“…Nitric oxide consumption (0.1 Ϯ 0.02 nmol⅐min⅐10 8 platelets Ϫ1 , after background correction; means Ϯ SD, n ϭ 3) was also observed following stimulation of platelets by the calcium ionophore, A23187 (300 nM) (Fig. 1b).…”

Section: Characterization Of ⅐ No Loss In Reaction Systems-nitricmentioning

confidence: 84%

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

O'Donnell¹,

Coles²,

Lewis³

et al. 2000

Journal of Biological Chemistry

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Nitric oxide ( ⅐ NO) plays a central role in vascular homeostasis via regulation of smooth muscle relaxation and platelet aggregation. Although mechanisms for ⅐ NO formation are well known, removal pathways are less well characterized, particularly in cells that respond to ⅐ NO through activation of soluble guanylate cyclase. Herein, we report that ⅐ NO is catalytically consumed by prostaglandin H synthase-1 (PGHS-1) through acting as a reducing peroxidase substrate. With purified ovine PGHS-1, ⅐ NO consumption requires peroxide (LOOH or H 2 O 2 ), with a K m (app) for 15(S)hydroperoxyeicosatetraenoic acid (HPETE) of 3.27 ؎ 0.35 M. During this, 2 mol ⅐ NO are consumed per mol HPETE, and loss of HPETE hydroperoxy group occurs with retention of the conjugated diene spectrum. Hydroperoxide-stimulated ⅐ NO consumption requires heme incorporation, is not inhibited by indomethacin, and is further stimulated by the reducing peroxidase substrate, phenol. PGHS-1-dependent ⅐ NO consumption also occurs during arachidonate, thrombin, or A23187 activation of platelets (1-2 M⅐min ؊1 for typical plasma platelet concentrations) and prevents ⅐ NO stimulation of platelet soluble guanylate cyclase. Platelet sensitivity to ⅐ NO as an inhibitor of aggregation is greater using a platelet-activating stimulus (U46619) that does not cause ⅐ NO consumption, indicating that this mechanism overcomes the anti-aggregatory effects of ⅐ NO. Catalytic consumption of ⅐ NO during eicosanoid synthesis thus represents both a novel proaggregatory function for PGHS-1 and a regulated mechanism for vascular ⅐ NO removal.In the vasculature, strict control of nitric oxide ( ⅐ NO) bioactivity is essential for both maintaining vascular tone and inhibiting platelet aggregation. Reaction with oxyhemoglobin (oxyHb) 1 is generally viewed to be the major fate of ⅐ NO generated in the vasculature. However, recent work has shown that erythrocyte sequestration of hemoglobin, combined with flow, decreases oxyHb reaction with ⅐ NO and thus renders it less effective at antagonizing ⅐ NO bioactivity in the vessel lumen (1, 2). Also, the biological half-life of ⅐ NO, when determined under oxyHb-free conditions (0.1-3 s), is far shorter than expected rates of ⅐ NO autooxidation (3, 4). Both of these observations indicate that cell-dependent catalytic scavenging reactions will play a role in regulating ⅐ NO signaling. Under pathological conditions of vascular dysfunction, accelerated ⅐ NO loss is often observed (5-7). In hypertensive states, a role for superoxide (O 2 . ) reacting with ⅐ NO to form peroxynitrite (ONOO Ϫ ) accounts for removal of a proportion of ⅐ NO. However, this is by no means the only mechanism for ⅐ NO removal because it is incompletely restored by O 2 . scavengers (7). Nitric oxide consumption by bacterial flavohemoglobins forms NO 3 Ϫ via reaction with the oxy form (8 -10) and is a proposed defense against "nitrosative stress." Recently, rabbit and human 15-lipoxygenases were also found to catalytically consume ⅐ NO, through reaction with an en...

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Section: Characterization Of ⅐ No Loss In Reaction Systems-nitricmentioning

confidence: 84%

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

O'Donnell¹,

Coles²,

Lewis³

et al. 2000

Journal of Biological Chemistry

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“…In the 16 O 2 derivative of the ferrous hemoglobin, a line was detected in the resonance Raman spectrum at 560 cm Ϫ1 , which shifted to 542 cm Ϫ1 in 18 O 2 (Fig. 3).…”

Section: Structural Features Of the Hbn Hemoglobinmentioning

confidence: 94%

“…Inside the chloroplast, the hemoglobin is localized, in part, in the same region as the thylakoid membranes, suggesting a possible involvement with the photosynthetic electron-transfer chains. Metabolic studies and gene disruption experiments suggest that hemoglobins belonging to the V. stercoraria family are involved in oxidative stress responses (15), metabolism of (16) and resistance to (17,18) nitric oxide, oxygen diffusion to terminal respiratory oxidases (19), and oxygen sensing (20).…”

mentioning

confidence: 99%

A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis

Couture

Yeh

Wittenberg

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

202

257

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Two putative hemoglobin genes, glbN and glbO, were recently discovered in the complete genome sequence of Mycobacterium tuberculosis H37Rv. Here, we show that the glbN gene encodes a dimeric hemoglobin (HbN) that binds oxygen cooperatively with very high affinity (P 50 ‫؍‬ 0.013 mmHg at 20°C) because of a fast combination (25 M ؊1 ⅐s ؊1 ) and a slow dissociation (0.2 s ؊1 ) rate. Resonance Raman spectroscopy and ligand association͞dissociation kinetic measurements, along with mutagenesis studies, reveal that the stabilization of the bound oxygen is achieved through a tyrosine at the B10 position in the distal pocket of the heme with a conformation that is unique among the globins. Physiological studies performed with Mycobacterium bovis bacillus Calmette-Guérin demonstrate that the expression of HbN is greatly enhanced during the stationary phase in aerobic cultures but not under conditions of limited oxygen availability. The results suggest that, physiologically, the primary role of HbN may be to protect the bacilli against reactive nitrogen species produced by the host macrophage.

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“…For example, it has been proposed that homocysteine reacts with nitrosylating compounds and acts as an NO antagonist because S. enterica strains carrying insertions in metL encoding aspartokinase IIhomoserine dehydrogenase II are hypersensitive to Snitrosothiol (7). The most prominent detoxifying entities that have been identified are the NO dioxygenase, NO denitrosylase, and NO reductase activities associated with the hmpA-encoded flavohemoglobin and the NO reductase activity associated with the norVW-encoded flavorubedoxin and flavorubedoxin reductase (8)(9)(10)(11)(12)(13)(14)(15)(16). Other detoxifying activities include NO reductase activity contributed by nfrA-encoded periplasmic cytochrome c nitrite reductase (17), and GSNO reductase activity associated with the adhC-encoded alcohol-acetaldehyde dehydrogenase (18).…”

mentioning

confidence: 99%

Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species

Mukhopadhyay

Zheng

Bedzyk

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

195

213

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We examined the genomewide transcriptional responses of Escherichia coli treated with nitrosylated glutathione or the nitric oxide (NO)-generator acidified sodium nitrite (NaNO 2) during aerobic growth. These assays showed that NorR, a homolog of NOresponsive transcription factors in Ralstonia eutrophus, and Fur, the global repressor of ferric ion uptake, are major regulators of the response to reactive nitrogen species. In contrast, SoxR and OxyR, regulators of the E. coli defenses against superoxide-generating compounds and hydrogen peroxide, respectively, have minor roles. Moreover, additional regulators of the E. coli response to reactive nitrogen species remain to be identified because several of the induced genes were regulated normally in norR, fur, soxRS, and oxyR mutant strains. We propose that the E. coli transcriptional response to reactive nitrogen species is a composite response mediated by the modification of multiple transcription factors containing iron or redox-active cysteines, some specifically designed to sense NO and its derivatives and others that are collaterally activated by the reactive nitrogen species.

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Role for the Salmonella Flavohemoglobin in Protection from Nitric Oxide

Cited by 164 publications

References 46 publications

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis

Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species

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