Protective role for the disulfide isomerase PDIA3 in methamphetamine neurotoxicity

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article numbere38909
JournalPloS one
Volume7
Issue number6
DOIs
StatePublished - Jun 8 2012

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protein disulfide-isomerase
Protein Disulfide-Isomerases
neurotoxicity
Methamphetamine
sulfides
Corpus Striatum
monkeys
neurons
Neurons
Haplorhini
brain
Brain
hippocampus
in vitro studies
Poisons
cytotoxicity
reactive oxygen species
Gene Expression Profiling
Neuroblastoma
Gene expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Protective role for the disulfide isomerase PDIA3 in methamphetamine neurotoxicity. / Pendyala, Gurudutt N; Ninemire, Carly; Fox, Howard S.

In: PloS one, Vol. 7, No. 6, e38909, 08.06.2012.

Research output: Contribution to journalArticle

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