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Methamphetamine-mediated endoplasmic reticulum (ER) stress induces type-1 programmed cell death in astrocytes via

Ankit Shah1, Anil Kumar1

  • 1Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.

Oncotarget
|June 22, 2016
PubMed

Insights

This study reveals that methamphetamine (MA) induces endoplasmic reticulum (ER) stress, leading to apoptosis and neurodegeneration. Targeting ER stress pathways offers a novel therapeutic strategy for methamphetamine-associated neurotoxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Methamphetamine (MA) causes neurotoxicity via inflammation and oxidative stress.
  • Endoplasmic reticulum (ER) stress-induced apoptosis is implicated in neurodegeneration, but its role in MA toxicity is unclear.

Purpose of the Study:

  • To investigate the effect of MA on ER stress and its involvement in apoptosis.
  • To elucidate the mechanistic details of MA-induced ER stress and apoptosis.

Main Methods:

  • SVGA astrocytes and mouse brain tissue were treated with MA.
  • ER stress markers (BiP, CHOP, IRE1α, ATF6, PERK) and apoptosis (MTT assay, TUNEL staining, caspase activation) were assessed.
  • siRNA was used to knock down ER stress pathway molecules.

Main Results:

  • MA treatment induced ER stress, evidenced by increased BiP and CHOP expression in astrocytes and mouse brains.
  • MA activated key ER stress pathways (IRE1α, ATF6, PERK).
  • Knockdown of ER stress proteins reduced MA-induced CHOP expression and apoptosis, including caspase-3 and caspase-9 activation.

Conclusions:

  • This study is the first to demonstrate MA-induced ER stress and its critical role in MA-mediated apoptosis.
  • Targeting ER stress pathways presents a novel therapeutic avenue for managing MA-induced neurotoxicity and neurodegenerative disorders.
Keywords:
CHOPER stressapoptosisastrocytesmethamphetamine

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