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Protective Role for the Disulfide Isomerase PDIA3 in Methamphetamine Neurotoxicity

ABSTRACT: Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE33707 | GEO | 2011/11/15

SECONDARY ACCESSION(S): PRJNA148485

REPOSITORIES: GEO

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Protective Role for the Disulfide Isomerase PDIA3 in Methamphetamine Neurotoxicity

Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain

2011-11-15 | E-GEOD-33707 | biostudies-arrayexpress

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Protective role for the disulfide isomerase PDIA3 in methamphetamine neurotoxicity.

Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Methamphetamine treatment of mice also increased striatal PDIA3 expression. Treatment of primary striatal neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations.

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Methamphetamine increases the proportion of SIV-infected microglia/macrophages, alters metabolic pathways, and elevates cell death pathways: a single-cell analysis

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The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity.

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0.6% Methamphetamine feeding experiments

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Transcription profiling by array of Drosophila fed methamphetamine

Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall omic response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals. For each sample, 20 virgin male flies were used to extract the mRNA. Three replicates were produced for each treatments. Two treatments were produced (control VS 0.6% 24 h meth-fed).

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