Inactivation of Cerebellar Nitric Oxide Synthase by Ethanol in Vitro

Fataccioli, Virginie; Gentil, Monique; Nordmann, Roger; Rouach, Hélène

doi:10.1093/oxfordjournals.alcalc.a008318

Cited by 25 publications

(19 citation statements)

References 22 publications

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“…0.05) inhibited NOS activity when assayed in the absence of exogenous BH4. A number of studies have demonstrated the essential role of exogenous BH4 in optimal assay of NOS activity [8,14,16]. Fataccioli et al [16] also observed a similar inhibitory effect of ethanol (25-200 mM ) on NOS in the cerebellum, and this inhibition could be alleviated by the addition of BH4 as well as L-arginine, the substrate for NOS.…”

Section: Discussionmentioning

confidence: 92%

“…A number of studies have demonstrated the essential role of exogenous BH4 in optimal assay of NOS activity [8,14,16]. Fataccioli et al [16] also observed a similar inhibitory effect of ethanol (25-200 mM ) on NOS in the cerebellum, and this inhibition could be alleviated by the addition of BH4 as well as L-arginine, the substrate for NOS. Besides serving as a cofactor for NOS, BH4 is also an important cofactor for hydroxylase of three aromatic L-amino acids responsible for the synthesis of catecholamines and serotonin [24].…”

Section: Discussionmentioning

confidence: 92%

“…Stimulation of the NMDA receptor is associated with increased intracellular Ca 2+ , which in turn is linked to an increase in a number of neuronal activities including neuronal NOS activity and enhancement of cGMP [6,10]. Thus, the NMDA-NOS-cGMP pathway has been implicated to play a crucial role in modulating synaptic plasticity in the brain [16] and may well be an important target of ethanol action.…”

Section: Discussionmentioning

confidence: 99%

“…Among many neurotransmitter systems in the central nervous system, the glutamatergic system, namely, the ionotropic N-methyl-D-aspartic acid (NMDA) receptors, is known to exhibit special sensitivity to the effect of ethanol [12,15,16,21]. Several studies have demonstrated a link between stimulation of the NMDA receptor and the increase in nitric oxide synthase (NOS) activity and cGMP production [6,10].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of N-Methyl-<i>D</i>-Aspartic Acid-Nitric Oxide Synthase in Rat Hippocampal Slices by Ethanol

Czapski¹,

Sun²,

Strosznajder³

2002

J Biomed Sci

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The ionotropic glutamatergic receptor system, especially the subtype mediated by N-methyl-D-aspartic acid (NMDA), is known to exhibit special sensitivity to the effect of ethanol. This is due partly to the ability of ethanol to modulate the production of nitric oxide through the NMDA-nitric oxide synthase (NOS) pathway. In this study, we examined the effects of ethanol on basal and NMDA-stimulated NOS activity in rat hippocampal slices by measuring the conversion of [¹⁴C]-arginine into [¹⁴C]-citrulline in an incubation system containing the necessary cofactors. Stimulation of hippocampal slices with NMDA (100 µM) enhanced NOS activity by 43% (n = 12). Although ethanol did not alter NOS activity when added to the incubation system during NMDA stimulation, it dose-dependently inhibited NMDA-NOS activity when added to the slices during the 90-min preincubation period. Further assay of NOS activity with brain cytosolic fraction indicated an inhibitory effect of ethanol (200 mM) when the assay was carried out in the absence of exogenous tetrahydrobiopterin (BH4), a redox-active cofactor for NOS. Incubation of brain homogenates resulted in a time-dependent increase in the levels of lipid peroxidation products, but ethanol did not further enhance these products. Taken together, these results provide evidence for the role of BH4 but not oxidative stress in the inhibitory effect of ethanol on NMDA-NOS activity in rat hippocampal slices.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of N-Methyl-<i>D</i>-Aspartic Acid-Nitric Oxide Synthase in Rat Hippocampal Slices by Ethanol

Czapski¹,

Sun²,

Strosznajder³

2002

J Biomed Sci

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“…Cyclic GMP activates cGMPdependent protein kinase, which phosphorylates a number of intracellular proteins, including several transcription factors (Gertzberg et al, 2000;Gudi et al, 1996;Mitani et al, 2000), thereby effecting gene expression (Shibata et al, 1998). Ethanol has been described to both inhibit (Fataccioli et al, 1997;Zima et al, 1998) and stimulate (Fitzgerald et al, 1995;Shi et al, 1998) NO pathways, but the role of NO in ethanol-induced effects is not clearly established. This study was undertaken to determine whether some of the effects of ethanol on mAChRs involve NO pathways.…”

mentioning

confidence: 99%

Role of Nitric Oxide in Ethanol‐Induced Up‐Regulation of Muscarinic Acetylcholine Receptors in SH‐SY5Y Cells

Caron

Alling

2001

Alcoholism Clin & Exp Res

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The results of this study suggest that the number of cell-surface mAChRs in SH-SY5Y cells may be correlated with changes in NO levels. The number of cell surface mAChRs decreased with NO-elevating treatment and increased with NO-lowering treatment. Because ethanol, which is known to up-regulate mAChRs in SH-SY5Y cells, also decreased NO levels and because nNOS inhibition and ethanol effects on mAChRs were not additive, it is conceivable that ethanol-induced up-regulation of mAChRs involves inhibition of nNOS.

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Mallory body formation by ethanol feeding in drug-primed mice

Zhang‐Gouillon

Yuan

et al. 1998

Hepatology

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Drug-primed mice, created by a 5-month feeding of diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC), followed by a 1-month withdrawal, were refed ethanol or isocaloric dextrose (control) diets intragastrically for 7 days. The formation of Mallory bodies (MBs) was monitored by immunofluorescence and immunoperoxidase microscopy using antibodies to cytokeratin and ubiquitin, and also by electron microscopy. The changes in cytokeratin 55 (CK55), ubiquitin conjugate, nuclear factor B (NFB) p65, NFB p50, inhibitor B␣, c-myc, tumor necrosis factor ␣, and cytochrome P450 2E1 (CYP2E1) contents were determined by Western blotting using appropriate antibodies. The messenger RNA (mRNA) for CYP2E1, cytokeratin, ubiquitin, hepatocyte growth factor activator, and tissue transglutaminase was quantitated. MBs were present at 5 to 7 days' postfeeding with ethanol, but not with dextrose. They developed in clusters of ''empty hepatocytes,'' where the cytokeratin antibody failed to recognize the typical filament structures seen in normal hepatocytes. MBs were larger and more numerous in the subcapsular region. Northern blots showed that CK55 mRNA was decreased by the ethanol treatment, but protein levels were increased, suggesting a decreased turnover of the cytokeratin. Likewise, the increase in CYP2E1 protein in the face of a lack of an increase in mRNA for CYP2E1 could be explained by a decreased turnover of this cytochrome. This is the first report of MB formation induced by ethanol ingestion in an experimental model. (HEPATOLOGY 1998;27:116-122.)The association between alcohol abuse and Mallory body (MB) formation in liver goes back to Mallory' s first report in 1911. 1 Mouse is the only species other than man in which MBs can be induced in response to a continuous feeding of various agents like griseofulvin and diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC). However, attempts to induce MBs by ethanol feeding in mice have been as yet unsuccessful, perhaps because of inappropriate experimental conditions. In recent years, we set up a drug-primed mouse model to study MB formation that involved a first feeding of the drug (griseofulvin or DDC) for 5 months, followed by drug withdrawal for 1 month, and a 7-day drug refeeding. [2][3][4] Most of the MBs disappear after the drug withdrawal, leaving only small dot-like MBs at the hepatocyte periphery. However, while it takes at least 3 months of continuous drug feeding before MBs appear in naive mice, 3,4 MBs reappear after only 3 days of refeeding in drug-primed mice. We have used this mouse model to show that heat shock performed in vivo leads to MB formation. 5 Therefore, it was of major interest to determine the response of these drug-primed mice to ethanol feeding. The experimental protocol included feeding via an intragastric indwelling tube to achieve good nutrition and to maintain high blood alcohol levels. 6 The results show for the first time that alcohol ''abuse'' can induce MBs in mice in a few days using a drug-primed model. MATERIALS...

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Inactivation of Cerebellar Nitric Oxide Synthase by Ethanol in Vitro

Cited by 25 publications

References 22 publications

Inhibition of N-Methyl-<i>D</i>-Aspartic Acid-Nitric Oxide Synthase in Rat Hippocampal Slices by Ethanol

Inhibition of N-Methyl-<i>D</i>-Aspartic Acid-Nitric Oxide Synthase in Rat Hippocampal Slices by Ethanol

Role of Nitric Oxide in Ethanol‐Induced Up‐Regulation of Muscarinic Acetylcholine Receptors in SH‐SY5Y Cells

Mallory body formation by ethanol feeding in drug-primed mice

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