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Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase and nitrite reductases.

Stefano GB, Kream RM - Med. Sci. Monit. (2011)

Bottom Line: Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes.Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine.The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, NY 11568-0210, USA. gstefano@sunynri.org

ABSTRACT
Our mini-review focuses on dual regulation of cellular nitric oxide (NO) signaling pathways by traditionally characterized enzymatic formation from L-arginine via the actions of NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes. Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine. It has become apparent that XOR possesses multi-functional enzymatic activities outside the realm of xanthine metabolism and a small but significant literature also established a compelling functional association between administered sodium nitrite, XOR activation, and pharmacologically characterized NO transductive effects in positive cardiovascular function enhanced pulmonary perfusion, and protection against ischemia/reperfusion injury and hypoxic damage and oxidative stress. Similar positive vascular and cellular effects were observed to be functionally associated with mitochondrial aldehyde dehydrogenase and cytochrome c/cytochrome c oxidase. The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below.

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Related in: MedlinePlus

Nitric oxide synthase (NOS) and nitrite reductases, e.g., xanthine oxidoreductase (XOR) physiological recruitment pathways. Nitric oxide synthase and nitrite reductases all can produce constitutive nitric oxide (NO) either alone or in synchrony to meet physiological demands in the modulation of tissue health. Their diminished reduction in NO production and ability to modulate their respective enzymes mediating their synthesis may contribute to pathophysiological sequelae. Given the presence of these parallel systems for NO production highlights the significance of baseline NO presence in “normal” health [93].
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f1-medscimonit-17-10-ra221: Nitric oxide synthase (NOS) and nitrite reductases, e.g., xanthine oxidoreductase (XOR) physiological recruitment pathways. Nitric oxide synthase and nitrite reductases all can produce constitutive nitric oxide (NO) either alone or in synchrony to meet physiological demands in the modulation of tissue health. Their diminished reduction in NO production and ability to modulate their respective enzymes mediating their synthesis may contribute to pathophysiological sequelae. Given the presence of these parallel systems for NO production highlights the significance of baseline NO presence in “normal” health [93].

Mentions: In support of the hypothesis stated above, there is considerable evidence that constitutively derived NO down-regulates the immunocyte-endothelial interaction [86,93,94]. NO has been shown to inhibit platelet and neutrophil aggregation [90]. In vitro, NO inhibits monocyte adhesion to porcine aortic endothelial cells [95]. In human vessels, the adherence of monocytes and granulocytes is reduced following the stimulation of cNOS [86,94,96] and, in the presence of NO, monocytes, granulocytes and endothelial cells become round and inactive [25,97]. These findings strongly indicate that NO can diminish the adherence and level of activation of leukocytes and endothelial cells. It also suggests these are phenomena that occur within a microenvironment given NO short-half life and the strength of the effect produced by many of these cells via autocrine and/paracrine signaling. It is now possible to add a functionally reinforcing mechanism whereby basal levels of cellular nitrite are recycled to active NO equivalents via the actions of XOR and accessory nitrite reductases upon physiological demand (Figure 1) [58,68].


Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase and nitrite reductases.

Stefano GB, Kream RM - Med. Sci. Monit. (2011)

Nitric oxide synthase (NOS) and nitrite reductases, e.g., xanthine oxidoreductase (XOR) physiological recruitment pathways. Nitric oxide synthase and nitrite reductases all can produce constitutive nitric oxide (NO) either alone or in synchrony to meet physiological demands in the modulation of tissue health. Their diminished reduction in NO production and ability to modulate their respective enzymes mediating their synthesis may contribute to pathophysiological sequelae. Given the presence of these parallel systems for NO production highlights the significance of baseline NO presence in “normal” health [93].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539480&req=5

f1-medscimonit-17-10-ra221: Nitric oxide synthase (NOS) and nitrite reductases, e.g., xanthine oxidoreductase (XOR) physiological recruitment pathways. Nitric oxide synthase and nitrite reductases all can produce constitutive nitric oxide (NO) either alone or in synchrony to meet physiological demands in the modulation of tissue health. Their diminished reduction in NO production and ability to modulate their respective enzymes mediating their synthesis may contribute to pathophysiological sequelae. Given the presence of these parallel systems for NO production highlights the significance of baseline NO presence in “normal” health [93].
Mentions: In support of the hypothesis stated above, there is considerable evidence that constitutively derived NO down-regulates the immunocyte-endothelial interaction [86,93,94]. NO has been shown to inhibit platelet and neutrophil aggregation [90]. In vitro, NO inhibits monocyte adhesion to porcine aortic endothelial cells [95]. In human vessels, the adherence of monocytes and granulocytes is reduced following the stimulation of cNOS [86,94,96] and, in the presence of NO, monocytes, granulocytes and endothelial cells become round and inactive [25,97]. These findings strongly indicate that NO can diminish the adherence and level of activation of leukocytes and endothelial cells. It also suggests these are phenomena that occur within a microenvironment given NO short-half life and the strength of the effect produced by many of these cells via autocrine and/paracrine signaling. It is now possible to add a functionally reinforcing mechanism whereby basal levels of cellular nitrite are recycled to active NO equivalents via the actions of XOR and accessory nitrite reductases upon physiological demand (Figure 1) [58,68].

Bottom Line: Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes.Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine.The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, NY 11568-0210, USA. gstefano@sunynri.org

ABSTRACT
Our mini-review focuses on dual regulation of cellular nitric oxide (NO) signaling pathways by traditionally characterized enzymatic formation from L-arginine via the actions of NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes. Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine. It has become apparent that XOR possesses multi-functional enzymatic activities outside the realm of xanthine metabolism and a small but significant literature also established a compelling functional association between administered sodium nitrite, XOR activation, and pharmacologically characterized NO transductive effects in positive cardiovascular function enhanced pulmonary perfusion, and protection against ischemia/reperfusion injury and hypoxic damage and oxidative stress. Similar positive vascular and cellular effects were observed to be functionally associated with mitochondrial aldehyde dehydrogenase and cytochrome c/cytochrome c oxidase. The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below.

Show MeSH
Related in: MedlinePlus