Positive Feedback Regulation of Human Inducible Nitric-oxide Synthase Expression by Ras Protein S-Nitrosylation

Lee, Martin; Choy, Jonathan C.

doi:10.1074/jbc.m113.475319

Cited by 27 publications

(12 citation statements)

References 69 publications

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“…The expressions of all NOS isoforms were enhanced by SNP and reduced by l-NAME suggesting thereby that NO may regulate NOS expression in ovary through feedback mechanism. This positive feedback control of eNOS, iNOS and nNOS expressions in fish may be similar to the recent report by Lee and Choy (2013) who have shown that NO augments iNOS expression in human lung epithelial cell line (A549) through S-nitrosylation of Ras and activation of PI3K and mTOR. Yuhanna and coworkers (1999) have also demonstrated the positive feedback control mechanism of eNOS expression by NO in human lung.…”

Section: Discussionsupporting

confidence: 89%

“…Similarly, NO is also known to inhibit the expressions of eNOS (Grumbach et al 2005) and nNOS in rat forebrain (De Alba et al 1999). Though it is suggested that NO may use varieties of mode and mechanism to exert these feedback control on NOS expressions (Griscavage et al 1993, De Alba et al 1999, Yuhanna et al 1999, Hinz et al 2000, Lee & Choy 2013, no study has been carried out so far to examine that how these feedback regulation of NOS expression by NO is terminated. The experimental design of the present study does not permit us to comment on this aspect, however, considering the wide-ranging biological actions of NO in tissuespecific manner, it may be proposed that perhaps the redox status and concentration of NO of the target cells, bestowed with specific cellular machinery and molecular ambience, altogether may decide the type of feedback effect of NO on the NOS expressions and their termination.…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide (NO) stimulates steroidogenesis and folliculogenesis in fish

Singh¹,

Lal²

2017

Reproduction

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The present study was undertaken to understand the physiological significance of the existence of nitric oxide synthase (NOS)/nitric oxide (NO) system in fish ovary. For this, two doses of NO donor, sodium nitroprusside (SNP, 25 µg and 50 µg) and NOS inhibitor, N-nitro-l-arginine methyl ester (l-NAME, 50 µg and 100 µg)/100 g body weight were administered during the two reproductive phases of reproductive cycle of the Clarias batrachus During the late-quiescence phase, high dose of l-NAME decreased the NO, testosterone, 17β-estradiol, vitellogenin contents in serum and ovary and activities of 5-ene-3β-hydroxysteroid dehydrogenases (3β-HSD) and 17β-hydroxysteroid dehydrogenases (17β-HSD) in ovary, whereas higher dose of SNP increased these parameters. l-NAME also reduced oocytes-I but increased perinucleolar oocytes in the ovary, whereas SNP treatment increased the number of advanced oocytes (oocytes-I and II) than the perinucleolar oocytes when compared with control ovary. During the mid-recrudescence phase, both doses of SNP increased NO, testosterone, 17β-estradiol and vitellogenin in serum and ovary; however, l-NAME treatment lowered their levels. The activities of ovarian 3β-HSD and 17β-HSD were also stimulated by SNP, but l-NAME suppressed their activities compared to the control. The SNP-treated ovaries were dominated by oocyte-II and III stages, whereas l-NAME-treated ovary revealed more perinucleolar oocytes and oocytes-I and practically no advanced oocytes. Expression of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) was augmented by the SNP and declined by l-NAME treatments as compared to the control. This study, thus, provides distinct evidence of NO-stimulated steroidogenesis, vitellogenesis and folliculogenesis in fish.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Nitric oxide (NO) stimulates steroidogenesis and folliculogenesis in fish

Singh¹,

Lal²

2017

Reproduction

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“…3 A and C and SI Appendix, Fig. S11), presumably owing to alterations in positive feedback mechanisms on the transcriptional level (38). Effective inhibition of NO release was reflected by widely preserved neuronal morphology (Fig.…”

Section: Lps or Ifn-γ Alone Induces Reactive Phenotypes In Microglia mentioning

confidence: 99%

TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ

Papageorgiou

Lewen

Galow

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

158

150

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Microglia (tissue-resident macrophages) represent the main cell type of the innate immune system in the CNS; however, the mechanisms that control the activation of microglia are widely unknown. We systematically explored microglial activation and functional microglia-neuron interactions in organotypic hippocampal slice cultures, i.e., postnatal cortical tissue that lacks adaptive immunity. We applied electrophysiological recordings of local field potential and extracellular K + concentration, immunohistochemistry, design-based stereology, morphometry, Sholl analysis, and biochemical analyses. We show that chronic activation with either bacterial lipopolysaccharide through Toll-like receptor 4 (TLR4) or leukocyte cytokine IFN-γ induces reactive phenotypes in microglia associated with morphological changes, population expansion, CD11b and CD68 up-regulation, and proinflammatory cytokine (IL-1β, TNF-α, IL-6) and nitric oxide (NO) release. Notably, these reactive phenotypes only moderately alter intrinsic neuronal excitability and gamma oscillations (30-100 Hz), which emerge from precise synaptic communication of glutamatergic pyramidal cells and fast-spiking, parvalbumin-positive GABAergic interneurons, in local hippocampal networks. Short-term synaptic plasticity and extracellular potassium homeostasis during neural excitation, also reflecting astrocyte function, are unaffected. In contrast, the coactivation of TLR4 and IFN-γ receptors results in neuronal dysfunction and death, caused mainly by enhanced microglial inducible nitric oxide synthase (iNOS) expression and NO release, because iNOS inhibition is neuroprotective. Thus, activation of TLR4 in microglia in situ requires concomitant IFN-γ receptor signaling from peripheral immune cells, such as T helper type 1 and natural killer cells, to unleash neurotoxicity and inflammation-induced neurodegeneration. Our findings provide crucial mechanistic insight into the complex process of microglia activation, with relevance to several neurologic and psychiatric disorders.hippocampus | microglia | neuronal activity | slice culture | Toll-like receptor

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“…NO can act as a neurotransmitter or is used to nitrosylate cysteine (S-nitrosylation) or tyrosine (Nytril-tyrosine) residues in a plethora of signalling molecules, thus changing their activity (Mehta et al, 2008;Lee & Choy, 2013;Suárez et al, 2009). We analysed the S-nitrosylation levels of proteins upon expression of Drp1-S637A, Drp1-K38A and GFP in PC12 cells, and as predicted, cell lysates expressing Drp1-S637A to increase mitochondrial fission exhibited an increase in S-nitrosylated proteins when compared with cell lysates expressing Drp1-K38A or GFP (Fig.…”

Section: Drp1 Activity Regulates Inos Levels In Dvcmentioning

confidence: 99%

Inhibition of Mitochondrial Fission and iNOS in the Dorsal Vagal Complex Protects from Overeating and Weight Gain

Patel

New

Griffiths

et al. 2020

Preprint

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AbstractThe dorsal vagal complex (DVC) senses changes in insulin levels and controls glucose homeostasis, feeding behaviour and body weight. Three days of high-fat diet (HFD) in rats is sufficient to induce insulin resistance in the DVC and impair its ability to regulate feeding behaviour. HFD-feeding is associated with increased mitochondrial fission in the DVC and fission is regulated by dynamin-related protein 1 (Drp1). Higher Drp1 activity can inhibit insulin signalling, although the exact mechanisms controlling body weight remain elusive. Here we show that Drp1 activation in DVC leads to higher body weight in rats and Drp1 inhibition in HFD-fed rats reduced body weight gain, cumulative food intake and adipose tissue, and prevented insulin resistance. Rats expressing active Drp1 in the DVC had higher levels of inducible nitric oxide synthase (iNOS) and knockdown of iNOS in the DVC of HFD-fed rats led to a reduction in body weight gain, cumulative food intake and adipose tissue, and prevented insulin resistance. In obese insulin-resistant animals, inhibition of mitochondrial fission or DVC iNOS knockdown restored insulin sensitivity and decreased food intake, body weight and fat deposition. Finally, we show that inhibiting mitochondrial fission in DVC astrocytes is sufficient to protect rats from developing HFD-dependent insulin resistance, hyperphagia, body weight gain and fat deposition. Our study uncovers new molecular and cellular targets for brain regulation of whole-body metabolism, which could inform new strategies to combat obesity and diabetes.

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Positive Feedback Regulation of Human Inducible Nitric-oxide Synthase Expression by Ras Protein S-Nitrosylation

Cited by 27 publications

References 69 publications

Nitric oxide (NO) stimulates steroidogenesis and folliculogenesis in fish

Nitric oxide (NO) stimulates steroidogenesis and folliculogenesis in fish

TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ

Inhibition of Mitochondrial Fission and iNOS in the Dorsal Vagal Complex Protects from Overeating and Weight Gain

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