No ·NO from NO synthase

Schmidt, Harald; Hofmann, Heinrich; Schindler, Ursula; Shutenko, Zhanna; Cunningham, David; Feelisch, Martin

doi:10.1073/pnas.93.25.14492

Cited by 348 publications

(288 citation statements)

References 50 publications

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“…Taken together, these results demonstrate that SOD-dependently generated endogenous NO can autoinhibit NOS activity. These findings are in accord with observations that NO formation from NOS can be detected only in the presence of SOD [27,28].…”

Section: Role Of Endogenous No and Nos-derived Products On Nos Activisupporting

confidence: 92%

“…Aqueous stock solutions of NO, ONOO − and HbO # were prepared as described [28,38]. The O # − d -generating system consisted of 250 µM hypoxanthine and up to 100 m-units\ml xanthine oxidase resulting in, for example, an O # − d flux at 0.75 munits\ml xanthine oxidase of 0.5 µM\min.…”

Section: No Onoo − Hbo 2 H 2 O 2 and O 2 − D -Generating System mentioning

confidence: 99%

“…Moreover, it remains controversial under which assay conditions NOS produces detectable levels of NO when measured either by electrochemical means or by EPR spec-troscopy [27][28][29]. If published results are taken together, there is some uncertainty with respect to a straightforward, NO-mediated autoinhibition of NOS.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the present study was therefore to investigate NOS autoinhibition further by taking into account the recent findings that (1) free NO can be detected only under certain assay conditions in NOS incubates [27,28,29] and (2) NOS-derived ROS can accumulate [32,33] and contribute to the enzyme 's autoregulation.…”

Section: Introductionmentioning

confidence: 99%

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Autoinhibition of neuronal nitric oxide synthase: distinct effects of reactive nitrogen and oxygen species on enzyme activity

Kotsonis

Frey

Fröhlich

et al. 1999

Biochemical Journal

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Nitric oxide (NO) synthases (NOSs), which catalyse the oxidation of -arginine to -citrulline and an oxide of nitrogen, possibly NO or nitroxyl (NO − ), are subject to autoinhibition by a mechanism that has yet to be fully elucidated. In the present study we investigated the actions of NO and other NOS-derived products as possible autoregulators of enzyme activity. With the use of purified NOS-I, -arginine turnover was found to operate initially at V max (0-15 min, phase I) although, despite the presence of excess substrate and cofactors, prolonged catalysis (15-90 min, phase II) was associated with a rapid decline in -arginine turnover. Taken together, these observations suggested that one or more NOS products inactivate NOS. Indeed, exogenously applied reactive nitrogen oxide species (RNSs) decreased V max during phase I, although with different potencies (NO − NO ONOO − ) and efficacies (NO NO − l ONOO − ). The NO scavengers oxyhaemoglobin (HbO # ; 100 µM) and 1H-imidazol-1-yloxy-2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-3-

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Section: Role Of Endogenous No and Nos-derived Products On Nos Activisupporting

confidence: 92%

Section: No Onoo − Hbo 2 H 2 O 2 and O 2 − D -Generating System mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autoinhibition of neuronal nitric oxide synthase: distinct effects of reactive nitrogen and oxygen species on enzyme activity

Kotsonis

Frey

Fröhlich

et al. 1999

Biochemical Journal

Self Cite

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“…The two states are both reactive nitrogen species, but the singlet state of NOcan react directly with thiols to form nitrosothiols. It has not been unequivocally substantiated as to which redox state, NO + or singlet NO -, is involved with S-nitrosylation in vivo; however, Schmidt et al (1996) presented evidence that nNOS produces NO -; therefore, it is speculated that singlet NO -is the most common redox state utilized during S-nitrosylation (Lipton et al, 1998). It is possible that triplet NO -is produced by iNOS, which is present in order to repair normal cellular damage or disassemble damaged cellular material.…”

Section: Nitroxyl Anion (Singlet and Triplet)mentioning

confidence: 99%

Nitric oxide and S‐nitrosylation: excitotoxic and cell signaling mechanism

Nelson

Connolly

McArthur

2003

Biology of the Cell

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This review focuses on the important physiological messenger, nitric oxide (NO), and its role in N-methyl-D-aspartate (NMDA) excitotoxicity. NO has been shown to be a key mediator of voltage-gated Ca +2 transmembrane proteins. It remains unclear whether NO is implicated during hypoxia, or ischemic/reperfusion injuries as a neuroprotective or neurodegenerative factor. Excitotoxicity results from the excessive stimulation of excitatory glutamate receptors within the CNS. This review maintains that the feed-forward pathway precipitated by oxidative stress is the discriminating factor in the neuroprotective or neurodegenerative actions of NO.

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Nitric oxide attenuates cellular hexose monophosphate shunt response to oxidants in articular chondrocytes and acts to promote oxidant injury

Clancy¹,

Abramson²,

Kohne³

et al. 1997

J. Cell. Physiol.

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Nitric oxide (NO) has been implicated in both cartilage degradation and cell survival. Importantly, NO has been shown, in a cell-type-dependent manner, to directly cause cell death or indirectly promote cell death by compromising the ability of cells to detoxify intra- or extracellular oxidants. In this study we examined the role of NO in the survival of bovine chondrocytes exposed to catabolic cytokines (interleukin-1 (IL-1); tumor necrosis factor [TNF]) with or without the addition of an exogenous oxidant stress (e.g., H2O2, HOOCl, etc.). The exposure of chondrocytes to a mixture of IL-1 and TNF (IL-1/TNF) results in the release of NO but did not alter cell viability. However, there was evidence of NO-dependent oxidative responses in the IL-1/TNF group, as we observed an increased level of intracellular oxidants as well as the appearance of a 55 kD nitrated protein which reflects the formation of peroxynitrite. We next analyzed viability with H2O2. The LD50 for IL-1/TNF-treated cells was 0.1 mM (vs. 1 mM for control). The enhanced sensitivity was completely reversed when cells were incubated with the NO synthase inhibitor 1-n5-1-iminoethylornithine (NIO). To test whether cell death was caused by compromising the ability of cells to detoxify extracellular oxidants, we examined the hexose monophosphate shunt (HMPS) response in cells given H2O2. Treatment of control cells with H2O2 resulted in a fourfold increase in HMPS activity. In contrast, IL-1/TNF cells exhibited no increase in HMPS activity. The attenuation of stimulated HMPS activity was reversed by the coaddition of NIO. Thus, these data indicate that 1) endogenous NO mediates cytokine-dependent susceptibility to oxidant injury and 2) this effect is in part due to impaired activation of the HMPS. In inflamed joints replete with cytokines and oxidants, NO may contribute to chondrocyte death and progressive joint destruction.

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No ·NO from NO synthase

Cited by 348 publications

References 50 publications

Autoinhibition of neuronal nitric oxide synthase: distinct effects of reactive nitrogen and oxygen species on enzyme activity

Autoinhibition of neuronal nitric oxide synthase: distinct effects of reactive nitrogen and oxygen species on enzyme activity

Nitric oxide and S‐nitrosylation: excitotoxic and cell signaling mechanism

Nitric oxide attenuates cellular hexose monophosphate shunt response to oxidants in articular chondrocytes and acts to promote oxidant injury

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