INVOLVEMENT OF OXIDATIVE AND L‐ARGININE‐NO PATHWAYS IN THE NEUROTOXICITY OF DRUGS OF ABUSE <i>IN VITRO</i>

Cerruti, Catherine; Sheng, Peilin; Ladenheim, Bruce; Cj, Epstein; Jl, Cadet

doi:10.1111/j.1440-1681.1995.tb02025.x

Cited by 21 publications

(17 citation statements)

References 4 publications

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“…Analysis of volume of infarction was further separated by measurements in right and left hemispheres. MA pretreatment significantly increased volume of infarction on the lesioned side ( Figure 3A; PϽ0.001, F (3,55) ϭ10.149, 1-way ANOVA, PϽ0.05, post hoc Newman-Keuls test). For group E, the MA plus MCA-CCA ligation plus GDNF (nϭ7) group, animals received intracerebral administration of GDNF (6ϫ10 Ϫ6 g) after 4 doses of MA.…”

Section: Ttc Stainingmentioning

confidence: 93%

“…Blotted RNAs were UV cross-linked. Blots were prehybridized for 2 hours at 37°C in a hybridization buffer that contained 12.5 mol/L formamide, 3 …”

Section: P53 Analysesmentioning

confidence: 99%

“…3,4 We and others have previously reported that ischemia and reperfusion can induce formation of reactive nitrogen compounds. 5,6 Because reactive oxygen and reactive nitrogen species form a toxic metabolite ONOO-, which activates poly(ADP-ribose) synthetase and damages cells, MA could facilitate the formation of ONOO-during stroke and cause increased neuronal damage.…”

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confidence: 97%

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Methamphetamine Potentiates Ischemia/Reperfusion Insults After Transient Middle Cerebral Artery Ligation

Wang

Hayashi

Chang

et al. 2001

Stroke

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Background and Purpose-Previous studies have indicated that both methamphetamine (MA) and ischemia/reperfusion injuries involve reactive oxygen species formation and activation of apoptotic mechanism. That MA could have a synergistic or additive effect with stroke-induced brain damage is possible. The purpose of the present study was to investigate whether administration of MA in vivo would potentiate ischemic brain injury. Methods-Adult CD-1 mice were pretreated with MA or saline. Each animal later was anesthetized with chloral hydrate and placed in a stereotaxic frame. A subset of animals received intracerebral administration of glial cell line-derived neurotrophic factor (GDNF). The right middle cerebral artery and bilateral carotids were transiently occluded for 45 minutes. Regional cerebral blood flow was measured by laser Doppler. Animals were sacrificed for triphenyltetrazolium chloride staining and p53 mRNA Northern blot assay after 24 hours of reperfusion. Cortical and striatal GDNF levels were assayed by ELISA. Results-We found that pretreatment with MA increased ischemia-induced cerebral infarction. Ischemia or MA alone enhanced p53 mRNA expression. Moreover, MA potentiated expression of p53 mRNA in the ischemic mouse brain. MA pretreatment decreased GDNF levels in ischemic striatum. Intracerebral administration of GDNF before ischemia reduced MA-facilitated infarction. Conclusions-Our data indicate that MA exacerbates ischemic insults in brain, perhaps through the inhibition of GDNF-mediated pathways and suggest that MA may antagonize endogenous neuroprotective pathways as part of its mechanism of action.

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Section: Ttc Stainingmentioning

confidence: 93%

“…Blotted RNAs were UV cross-linked. Blots were prehybridized for 2 hours at 37°C in a hybridization buffer that contained 12.5 mol/L formamide, 3 …”

Section: P53 Analysesmentioning

confidence: 99%

mentioning

confidence: 97%

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Methamphetamine Potentiates Ischemia/Reperfusion Insults After Transient Middle Cerebral Artery Ligation

Wang

Hayashi

Chang

et al. 2001

Stroke

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“…Nitric oxide has been implicated as a mediator of neurotoxicity (Cerruti et al, 1995), and its involvement in the pathophysiology of neuronal cell death has received considerable attention. Several studies have demonstrated that nitric-oxide synthase (NOS) inhibitors provide protection against methamphetamine and MDMA-induced dopaminergic and serotonergic neurotoxicity in rodents.…”

mentioning

confidence: 99%

Evidence for the Involvement of Nitric Oxide in 3,4-Methylenedioxymethamphetamine-Induced Serotonin Depletion in the Rat Brain

Darvesh

Yamamoto

Gudelsky

2004

J Pharmacol Exp Ther

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Production of reactive oxygen and/or nitrogen species has been thought to contribute to the long-term depletion of brain dopamine and serotonin (5-HT) produced by amphetamine derivatives, i.e., methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). In the present study, the effects of nitric-oxide synthase (NOS) inhibitors were examined on the long-term depletion of striatal dopamine and/or 5-HT produced by the local perfusion of malonate and MDMA or the systemic administration of MDMA. The effect of MDMA on nitric oxide formation and nitrotyrosine concentration also was determined. Perfusion with MDMA and malonate resulted in a 34% reduction of 5-HT and 49% reduction of dopamine concentrations in the striatum. The systemic administration of NOS inhibitors, N-nitro-L-arginine methyl ester hydrochloride and S-methyl-Lthiocitrulline (S-MTC), and the peroxynitrite decomposition catalyst Fe(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride attenuated the MDMA-and malonate-induced depletion of striatal dopamine and 5-HT. S-MTC also attenuated the depletion of 5-HT in the striatum produced by the systemic administration of MDMA without attenuating MDMA-induced hyperthermia. Additionally, the systemic administration of MDMA significantly increased the formation of nitric oxide and the nitrotyrosine concentration in the striatum. These results support the conclusion that MDMA produces reactive nitrogen species in the rat that contribute to the neurotoxicity of this amphetamine analog.

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“…Many amphetamines are now known to produce various ROS and NO in brain (Abekawa et al, 1995;Bow yer et al, 1995;Cerruti et al, 1995;Colado and Green, 1995;Giovanni et al, 1995;Hirata et al, 1995;Di Monte et al, 1996). If the focus is restricted to NO, a priori conclusions about its effects on cells or proteins cannot be made.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of the Inactivation of Tryptophan Hydroxylase by Nitric Oxide: Attack on Critical Sulfhydryls that Spare the Enzyme Iron Center

Kuhn

Arthur²

1997

J. Neurosci.

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Tryptophan hydroxylase (TPH), the initial and rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin (5-HT), is irreversibly inactivated by nitric oxide (NO). We have expressed brain TPH as a recombinant glutathione-Stransferase fusion protein and delineated the catalytic domain of the enzyme as the region spanning amino acids 99-444. Highly purified TPH catalytic core, like the native enzyme from brain, is inactivated by NO in a concentration-dependent manner. Removal of iron from TPH produces an apoenzyme with low activity that can be reconverted to its highly active holoform by the addition of ferrous iron. Apo-TPH exposed to NO cannot be reactivated by iron. Treatment of holo-TPH (ironloaded) with the disulfide 5,5Ј-dithio-bis (2-nitrobenzoic acid) (DTNB) causes an inactivation of TPH that is readily reversed by dithiothreitol (DTT). DTNB-treated TPH [sulfhydryl (SH)-protected] exposed to NO is returned to full activity by thiol reduction with DTT. The inactivation of native TPH by NO cannot be reversed by either iron or DTT. These data indicate that NO inactivates TPH by selective action on critical SH groups (i.e., cysteine residues) while sparing catalytic iron sites within the enzyme. The results are interpreted with reference to the substituted amphetamines, which are neurotoxic to 5-HT neurons, that inactivate TPH in vivo and are now known to produce NO and other reactive oxygen species in vivo. Key words: tryptophan hydroxylase; nitric oxide; sulfhydryls; catalytic iron site; serotonin; neurotoxic amphetaminesTryptophan hydroxylase [EC 1.14.16.4; L-tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating)] (TPH) is the initial and rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin (5-HT) (Jequier et al., 1967). The synthesis of 5-HT can proceed only through this enzymecatalyzed step. The activity of TPH controls the amount of 5-HT produced and released from neurons (Gartside et al., 1992;Oluyomi et al., 1994), indicating that this enzyme regulates not just 5-HT synthesis but its f unction as well. As a neurotransmitter, 5-HT mediates pain, sleep, thermoregulation, and food intake. From a clinical perspective, altered 5-HT f unction has been implicated in depression, obsessive-compulsive disorder, autism, and impulsive self-destructive behaviors such as aggression, suicide, and drug taking (Schatzberg and Nemeroff, 1995).Selected amphetamines have profound effects on the 5-HT neuronal system. Methylenedioxymethamphetamine (ecstasy) (MDM A) and p-chloroamphetamine cause extensive destruction of 5-HT neurons. An early manifestation of their effects is a significant inactivation of TPH (for reviews, see Gibb et al., 1993;Steele et al., 1994;Seiden and Sabol, 1996). The mechanisms underlying these effects on TPH are not known, but emerging data implicate drug-induced production of reactive oxygen species (ROS) and nitric oxide (NO). The cellular effects of ROS or NO cannot be predicted a priori: NO can be toxic to some cells (Lipton et al., 1993;Da...

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INVOLVEMENT OF OXIDATIVE AND L‐ARGININE‐NO PATHWAYS IN THE NEUROTOXICITY OF DRUGS OF ABUSE IN VITRO

Cited by 21 publications

References 4 publications

Methamphetamine Potentiates Ischemia/Reperfusion Insults After Transient Middle Cerebral Artery Ligation

Methamphetamine Potentiates Ischemia/Reperfusion Insults After Transient Middle Cerebral Artery Ligation

Evidence for the Involvement of Nitric Oxide in 3,4-Methylenedioxymethamphetamine-Induced Serotonin Depletion in the Rat Brain

Molecular Mechanism of the Inactivation of Tryptophan Hydroxylase by Nitric Oxide: Attack on Critical Sulfhydryls that Spare the Enzyme Iron Center

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