Hemoglobins dioxygenate nitric oxide with high fidelity

Gardner, Paul R.; Gardner, Anne M.; Brashear, Wayne T.; Suzuki, Tomohiko; Hvitved, Angela N.; Setchell, Kenneth D.R.; Olson, John S.

doi:10.1016/j.jinorgbio.2005.12.012

Cited by 116 publications

(124 citation statements)

References 110 publications

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“…The relatively high nitrate production from MNX was attributed to MNX denitrosation and subsequent oxidation of the resulting NO to nitrate. It has been reported that some microbial flavohemoglobin (flavoHb) can exhibit nitric oxide dioxygenase activity (30) and oxidize NO to NO 3 -using 18 O 2 -labeled oxyheme (flavoHb(Fe III -18 O 2 )) prepared from Escherichia coli (35). In this respect, when we incubated MNX with DN22 in the presence of 18 O 2 we detected NO 3 -with two mass ions: a major one at m/z 66 Da incorporating two 18 O atoms and another minor one at m/z 64 Da incorporating only one 18 O ( Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

Halasz

Manno

Strand

et al. 2010

Environ. Sci. Technol.

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Previously we demonstrated that Rhodococcus sp. strain DN22 can degrade RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) aerobically via initial denitration. The present study describes the role of oxygen and water in the key denitration step leading to RDX decomposition using 18 O 2 and H 2 18 O labeling experiments. We also investigated degradation of MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine) with DN22 under similar conditions. DN22 degraded RDX and MNX giving NO 2

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Section: Resultsmentioning

confidence: 99%

Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

Halasz

Manno

Strand

et al. 2010

Environ. Sci. Technol.

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“…Furthermore, recent data establish both myoglobin and hemoglobin as intrinsic nitrite reductases, with critical roles in regulating hypoxic nitric oxide signaling (56)(57)(58). Hemoglobin was shown to function as a nitric oxide dioxygenase by controlling O 2 binding, further emphasizing a critical role in nitric oxide metabolism and detoxification (59). Other cellular hemoglobins, and specifically neuroglobin, were shown to be cytoprotective during hypoxia and ischemia, potentially by modulating the mRNA expression of hypoxic response genes (60,61).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Up-Regulates Expression of Hemoglobin in Alveolar Epithelial Cells

Grek

Newton²,

Spyropoulos³

et al. 2011

Am J Respir Cell Mol Biol

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Alveolar epithelial cells are directly exposed to acute and chronic fluctuations in alveolar oxygen tension. Previously, we found that the oxygen-binding protein hemoglobin is expressed in alveolar Type II cells (ATII). Here, we report that ATII cells also express a number of highly specific transcription factors and other genes normally associated with hemoglobin biosynthesis in erythroid precursors. Because hypoxia-inducible factors (HIFs) were shown to play a role in hypoxia-induced changes in ATII homeostasis, we hypothesized that the hypoxia-induced increase in intracellular HIF exerts a concomitant effect on ATII hemoglobin expression. Treatment of cells from the ATII-like immortalized mouse lung epithelial cell line-15 (MLE-15) with hypoxia for 20 hours resulted in dramatic increases in cellular levels of HIF-2a protein and parallel significant increases in hemoglobin messenger RNA (mRNA) and protein expression, as compared with that of control cells cultured in normoxia. Significant increases in the mRNA of globin-associated transcription factors were also observed, and RNA interference (RNAi) experiments demonstrated that the expression of hemoglobin is at least partially dependent on the cellular levels of globin-associated transcription factor isoform 1 (GATA-1). Conversely, levels of prosurfactant proteins B and C significantly decreased in the same cells after exposure to hypoxia. The treatment of MLE-15 cells cultured in normoxia with prolyl 4-hydroxylase inhibitors, which mimic the effects of hypoxia, resulted in increases of hemoglobin and decreases of surfactant proteins. Taken together, these results suggest a relationship between hypoxia, HIFs, and the expression of hemoglobin, and imply that hemoglobin may be involved in the oxygen-sensing pathway in alveolar epithelial cells.Keywords: hemoglobin; alveolar epithelial cells; hypoxia; hypoxiainducible factor Pulmonary hypoxia occurs under both physiologic and pathologic conditions. In fact, a hypoxic environment is necessary for proper embryonic lung development, by promoting the formation of microvasculature and epithelial branching morphogenesis (the average fetal blood O 2 fraction is z2-5%) (1-3). However, postnatal decreases in alveolar oxygen tension as a result of pulmonary disease disrupt alveolar homeostasis. High-altitude ascent, pathologic conditions resulting in inadequate respiration, pulmonary edema after acute lung injury, or congestive heart failure may all result in decreased oxygen tension. Alveolar Type II (ATII) cells represent approximately two thirds of epithelial cell numbers, and are of special clinical interest because of their role in the production, secretion, and recycling of pulmonary surfactant (4). In addition, ATII cells differentiate into Type I (ATI ) cells upon epithelial injury, and also act to clear fluid from the alveolar space. Although numerous studies evaluated the effects of hypoxia on the pulmonary endothelium, few sought to identify hypoxia-regulated genes in alveolar epithelial cells.Our previous stu...

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“…Many of the above mechanisms implicate metalloproteins as modulators of NO bioavailability among which the role of oxyglobins such as oxyhemoglobin and oxymyoglobin have been already highlighted (16). One of the primary mechanisms is the dioxygenation of NO to form nitrate and the ferric (Fe(III)) form of the protein.…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Cytoglobin Is Expressed in the Vasculature and Regulates Cell Respiration and Proliferation via Nitric Oxide Dioxygenation

Halligan

Jourd’heuil

2009

Journal of Biological Chemistry

108

121

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Disposition of the second messenger nitric oxide (NO) in mammalian tissues occurs through multiple pathways including dioxygenation by erythrocyte hemoglobin and red muscle myoglobin. Metabolism by a putative NO dioxygenase activity in non-striated tissues has also been postulated, but the exact nature of this activity is unknown. In the present study, we tested the hypothesis that cytoglobin, a newly discovered hexacoordinated globin, participates in cell-mediated NO consumption. Stable expression of small hairpin RNA targeting cytoglobin in fibroblasts resulted in decreased NO consumption and intracellular nitrate production. These cells were more sensitive to NO-induced inhibition of cell respiration and proliferation, which could be restored by re-expression of human cytoglobin. We also demonstrated cytoglobin expression in adventitial fibroblasts as well as vascular smooth muscle cells from various species including human and found that cytoglobin was expressed in the adventitia and media of intact rat aorta. These results indicate that cytoglobin contributes to cell-mediated NO dioxygenation and represents an important NO sink in the vascular wall. Nitric oxide (NO)2 plays a central role in the vasculature and regulates oxygen supply by relaxing smooth muscle and inhibiting mitochondrial respiration. NO is produced by nitric-oxide synthase and through mobilization of storage pools such as nitrite. Less is known on the mechanism of NO inactivation and removal in the vasculature, although it would be surprising that blood vessels rely on nonspecific chemical reactions to control its disposition.Blood removes NO through reaction with excess oxyhemoglobin in erythrocytes, but diffusional barriers such as the red blood cell-free layer near the vessel wall allow autocrine NO to occur in significant amounts in the vascular wall (1, 2). In striated muscles, oxymyoglobin is an NO scavenger, and studies using transgenic mice lacking myoglobin have demonstrated a role for oxymyoglobin in attenuating NO-mediated cardiac dysfunction (3, 4). In contrast, NO inactivation in non-striated tissues is poorly understood, and examination of NO consumption in various cells suggests mechanisms that differ in NO saturation, oxygen and cyanide sensitivity, and product formation (5-8). Specific pathways include increased partition of NO in cell membranes (7) and consumption of NO by cytochrome c oxidase (9 -11), NADPH oxidase (12), 15-lipoxygenase (13), prostaglandin-H synthase (14), and myeloperoxidase (15).Many of the above mechanisms implicate metalloproteins as modulators of NO bioavailability among which the role of oxyglobins such as oxyhemoglobin and oxymyoglobin have been already highlighted (16). One of the primary mechanisms is the dioxygenation of NO to form nitrate and the ferric (Fe(III)) form of the protein. The recent discovery of two new mammalian globins, cytoglobin and neuroglobin, would suggest that the reactions of NO with globins are not limited to red blood cells and striated muscles but could extend to other ...

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Hemoglobins dioxygenate nitric oxide with high fidelity

Cited by 116 publications

References 110 publications

Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

Biodegradation of RDX and MNX with Rhodococcus sp. Strain DN22: New Insights into the Degradation Pathway

Hypoxia Up-Regulates Expression of Hemoglobin in Alveolar Epithelial Cells

Cytoglobin Is Expressed in the Vasculature and Regulates Cell Respiration and Proliferation via Nitric Oxide Dioxygenation

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