Widespread tissue distribution, species distribution and changes in activity of Ca<sup>2+</sup>‐dependent and Ca<sup>2+</sup>‐independent nitric oxide synthases

Salter, Mark; Knowles, Richard G.; Moncada, Salvador

doi:10.1016/0014-5793(91)81123-p

Cited by 625 publications

(345 citation statements)

References 30 publications

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“…The activity of the calcium-dependent NOS was calculated from the difference between L-[ 14 C]citrulline produced from control samples and samples containing ethylene glycolbis(aminoethyl ether) N,N,N 0 -tetraacetic acid (EGTA, 1 mM); the activity of the calcium-independent isoform was determined from the difference between samples with EGTA and samples containing 1 mM N G -monomethyl-Larginine (L-NMMA). The [ 14 C]-bound radioactivity was counted using a liquid scintillation counter (Beckman LS-6500) (Salter et al, 1991;Rees et al, 1995 (Cortas and Wakid, 1990) and NO 2 À was determined by a colorimetric assay based on the Griess reaction (Green et al, 1982) in a Thermomax s microplate reader (Molecular Devices). The measurement of NO x À levels has been found to be a reliable technique to determine the synthesizing capacity of NOS in the brain (Salter et al, 1996).…”

Section: No Synthase Activitymentioning

confidence: 99%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

135

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Cyclooxygenase (COX) is the rate-limiting enzyme in the metabolism of arachidonic acid into prostanoids. Although it is constitutively expressed in brain neurons, the inducible isoform (COX-2) is also upregulated in pathological conditions such as seizures, ischemia or some degenerative diseases. To assess whether COX-2 is regulated after stress, we have used adult male Wistar rats, some of which were immobilized during 6 h. An increase in PGE 2 concentration occurs in brain cortex after 2-6 h of the onset of stress as well as an enhancement of COX-2 protein. Immunohistochemical studies indicate that COX-2 is expressed in the cortex and hippocampus after stress in cells with morphology of neurons. Administration of PDTC (150 mg/kg), an inhibitor of the transcription factor NF-kB or MK-801 (0.2 mg/kg), an N-methyl-D-aspartate receptor blocker, prevents both stress-induced increase in COX-2 activity and protein levels, suggesting an implication of these factors in the mechanism by which stress induces COX-2 in brain. To assess if COX-2 accounts for the oxidative status seen in brain after stress, a group of animals were i.p. injected with NS-398, a specific COX-2 inhibitor 1 h prior to the onset of stress. NS-398 (5 mg/kg) decreases stress-induced malondialdehyde accumulation in cortex as well as prevents the stressinduced oxidation of glutathione. Finally, NS-398 reduced Ca 2+ -independent inducible nitric oxide synthase (iNOS, NOS-2) activity and lowered the stress-induced accumulation of NO metabolite levels in cortex. These effects of NS-398 seem to be due to the specific inhibition of COX-2, since it has no effect on stress-induced corticosterone release, glutamate release, and NF-kB activation. These findings are discussed as possible damaging and/or adaptive roles for stress-induced COX-2 in the brain.

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Section: No Synthase Activitymentioning

confidence: 99%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

135

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“…Popliteal lymph nodes from C57BL/6 mice treated with anti-TNF- § , nIgG or saline were collected at the 2nd, 6th and 12th week after infection with L. major, and iNOS activity was determined by measuring the formation of [ 14 C]citrulline as previously described [28]. iNOS activity was expressed as pmol citrulline/mg protein/h.…”

Section: Inos Activity Assaymentioning

confidence: 99%

TNF‐α mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis

et al. 2003

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Leishmania major infection in C57BL/6 mice is controlled by the activation of a Th1 response and nitric oxide (NO) production by macrophages. TNF- § is considered one of the most important cytokines involved in this response. In the present study, we investigated the expression of nitric oxide synthase (iNOS) in the inflammatory cells present in the lesion and draining lymph nodes, and the cytokine production by lymph node cells in animals treated with anti-TNF- § . Our results demonstrated that mice treated with anti-TNF- § presented an increase in the number of parasites and the size of lesion, but they were able to control the infection. The increase in the lesion size correlated to the reduction of iNOS activity in the draining lymph nodes. Furthermore, the anti-TNF- § treatment also reduced the expression of iNOS in the macrophages, but did not affect the iNOS expression in the neutrophils. The anti-TNF- § mAb did not reduce the iNOS expression in IFN-+ -stimulated L. major infected neutrophils in vitro. Anti-TNF- § mAb treatment caused an increase in the production of IFN-+ and IL-10 by the lymph node cells from infected mice. Consequently, these results suggest that neutrophils do not respond to anti-TNF- § treatment and might be a source of NO to control L. major infection under these experimental conditions.

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“…NO produced by the inducible enzyme is a major mediator of macrophage cytotoxicity [7][8][9] and has been implicated as a mediator in septic shock [10][11][12] and inflammation. The stable end products of NO are NO~ and NO~ and these have previously been employed as a measure of NO production [13].…”

Section: Introductionmentioning

confidence: 99%

l‐Arginine depletion by arginase reduces nitric oxide production in endotoxic shock: an electron paramagnetic resonance study

et al. 1995

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Nitric oxide (NO) synthesis was measured in the liver, lung, spleen and kidney of Iipopolysaccharide-treated male rats using the nitric oxide spin trap, iron (ll)-dlethyldithiocarbamate (FeDETC2). Nitric oxide formation in vlvo was determined by the Increase in intensity of the characteristic triplet hyperflne EPR spectrum of [NO-FeDETC,]. Intravenous bovine liver arginase, nt a dose which completely depleted circniating arginlne, significantly reduced the formation of nitric oxide in these tissues. The general decrease in NO levels was confirmed by the decrease in plasma nitrite levels. These results directly demonstrate that NO formation in endotoxic shock depends on extracellular arginine; depletion of plasma arginine may be a useful therapeutic strategy.

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Widespread tissue distribution, species distribution and changes in activity of Ca²⁺‐dependent and Ca²⁺‐independent nitric oxide synthases

Cited by 625 publications

References 30 publications

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

TNF‐α mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis

l‐Arginine depletion by arginase reduces nitric oxide production in endotoxic shock: an electron paramagnetic resonance study

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Widespread tissue distribution, species distribution and changes in activity of Ca2+‐dependent and Ca2+‐independent nitric oxide synthases

Cited by 625 publications

References 30 publications

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

TNF‐α mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis

l‐Arginine depletion by arginase reduces nitric oxide production in endotoxic shock: an electron paramagnetic resonance study

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Widespread tissue distribution, species distribution and changes in activity of Ca²⁺‐dependent and Ca²⁺‐independent nitric oxide synthases