Oxidation of N-hydroxyguanidines by copper(II): model systems for elucidating the physiological chemistry of the nitric oxide biosynthetic intermediate N-hydroxyl-l-arginine

Cho, Jennifer Y.; Dutton, Andrew S.; Miller, Thomas W.; Houk, K. N.; Fukuto, Jon M.

doi:10.1016/s0003-9861(03)00335-7

Cited by 29 publications

(30 citation statements)

References 47 publications

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“…Since HOCl is likely generated more slowly from MPO than when it is added bolus, we suspect that unreacted NOHA may be quenching HNO as it is produced, consistent with the previous observation that N-hydroxyguanidines can react with HNO [32].…”

Section: Oxidation Of N-hydroxy-l-arginine By Myeloperoxidasesupporting

confidence: 89%

“…In addition, research has demonstrated that NOHA can be chemically oxidized to produce either NO or HNO depending on the oxidant used [29][30][31]. Likewise, related N-hydroxyguanidines have been shown to form either HNO or NO depending upon the oxidative conditions [32]. The HNO-producing pathway presumably involves a nitroso intermediate and the corresponding production of a cyanamide derivative (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO)

Cline

Chavez

Toscano

2013

Journal of Inorganic Biochemistry

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Section: Oxidation Of N-hydroxy-l-arginine By Myeloperoxidasesupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO)

Cline

Chavez

Toscano

2013

Journal of Inorganic Biochemistry

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“…NOHA is a naturally occurring intermediate product of endothelial nitric oxide synthase that is metabolized to nitric oxide, thus serving as its donor. 25,26 We used the concentration of NOHA that in preliminary studies showed no induction of hypotension or oxidative stress (not shown). Indeed, in vitro studies demonstrated that NOHA suppresses vectorial movements of lysosomes after the application of LPS ( Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Exocytosis of Endothelial Lysosome-Related Organelles Hair-Triggers a Patchy Loss of Glycocalyx at the Onset of Sepsis

Zullo

Fan

Azar

et al. 2016

The American Journal of Pathology

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Sepsis is a systemic inflammatory syndrome induced by bacterial infection that can lead to multiorgan failure. Endothelial surface glycocalyx (ESG) decorating the inner wall of blood vessels is a regulator of multiple vascular functions. Here, we tested a hypothesis that patchy degradation of ESG occurs early in sepsis and is a result of exocytosis of lysosome-related organelles. Time-lapse video microscopy revealed that exocytosis of Weibel-Palade bodies and secretory lysosomes occurred a few minutes after application of lipopolysaccharides to endothelial cells. Two therapeutic maneuvers, a nitric oxide intermediate, NG-hydroxy-L-arginine, and culture media conditioned by endothelial progenitor cells reduced the motility of lysosome-related organelles. Confocal and stochastic optical reconstruction microscopy confirmed the patchy loss of ESG simultaneously with the exocytosis of lysosome-related organelles and Weibel-Palade bodies in cultured endothelial cells and mouse aorta. The loss of ESG was blunted by pretreatment with NG-hydroxy-L-arginine or culture media conditioned by endothelial progenitor cells. Moreover, these treatments resulted in a significant reduction in deaths of septic mice. Our data support the hypothesis assigning to stress-induced exocytosis of these organelles the role of a hair-trigger for local degradation of ESG that initiates leukocyte infiltration, increase in vascular permeability, and partially accounts for the later rates of morbidity and mortality. Sepsis is a systemic inflammatory syndrome induced by bacterial infection that can lead to multiorgan failure. It afflicts >700,000 individuals annually in the United States alone, has mortality rates of 30%, and is the 11th leading cause of death. One of the key molecular causes of Gram-negative septicemia is endotoxin that consists of lipopolysaccharides (LPSs) bound with high affinity to LPS-binding glycoprotein. Complex LPS-binding glycoprotein is recognized by cognate receptor Toll-like receptor 4 and co-receptor CD14 on monocytes/macrophages and endothelial cells. 1 Considering the systemic nature of septicemia, vascular endothelium represents the first line of exposure to bacterial endotoxins. 2 It responds to endotoxins with a complex system of danger signals, which are chronologically sequenced and spatially propagated. 3 Functionally, these waves of danger signaling tend to secure proper organismal responses, both proinflammatory and anti-inflammatory.Among the earliest responses of activated endothelial cells to endotoxin are exocytosis of Weibel-Palade bodies (WPBs) and secretory lysosomes. 4 WPBs are rod-shaped members of lysosome-related organelles (0.2 mm by 2 to 3

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“…A number of chemical studies indicate that HNO can be generated from oxidative degradation of N-hydroxy-l-arginine. [30][31][32] This has the potential to be a physiologically relevant process since N-hydroxy-l-arginine has been detected at significant levels (up to 20 mm) in plasma [33,34] and is released by some cells in vitro. [35] HNO might also be generated by nitric oxide synthase directly [36,37] especially when it is deplete of one of its prosthetic groups, tetrahydrobiopterin.…”

Section: Hno Biologymentioning

confidence: 99%