Role of endoplasmic reticulum (ER) stress in cocaine-induced microglial cell death

Blaise Mathias Costa, Honghong Yao, Lu Yang, Shilpa J Buch

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

While it has been well-documented that drugs of abuse such as cocaine can enhance progression of human immunodeficiency virus (HIV)-associated neuropathological disorders, the underlying mechanisms mediating these effects remain poorly understood. The present study was undertaken to examine the effects of cocaine on microglial viability. Herein we demonstrate that exposure of microglial cell line-BV2 or rat primary microglia to exogenous cocaine resulted in decreased cell viability as determined by MTS and TUNEL assays. Microglial toxicity of cocaine was accompanied by an increase in the expression of cleaved caspase-3 as demonstrated by western blot assays. Furthermore, increased microglial toxicity was also associated with a concomitant increase in the production of intracellular reactive oxygen species, an effect that was ameliorated in cells pretreated with NADPH oxidase inhibitor apocynin, thus emphasizing the role of oxidative stress in this process. A novel finding of this study was the involvement of endoplasmic reticulum (ER) signaling mediators such as PERK, Elf2α, and CHOP, which were up regulated in cells exposed to cocaine. Reciprocally, blocking CHOP expression using siRNA ameliorated cocaine-mediated cell death. In conclusion these findings underscore the importance of ER stress in modulating cocaine induced microglial toxicity. Understanding the link between ER stress, oxidative stress and apoptosis could lead to the development of therapeutic strategies targeting cocaine-mediated microglial death/dysfunction.

Original languageEnglish (US)
Pages (from-to)705-714
Number of pages10
JournalJournal of Neuroimmune Pharmacology
Volume8
Issue number3
DOIs
StatePublished - Jun 1 2013

Fingerprint

Endoplasmic Reticulum Stress
Cocaine
Cell Death
Oxidative Stress
NADPH Oxidase
In Situ Nick-End Labeling
Microglia
Street Drugs
Caspase 3
Endoplasmic Reticulum
Small Interfering RNA
Reactive Oxygen Species
Cell Survival
Western Blotting
HIV
Apoptosis
Cell Line

Keywords

  • BV2 cells
  • CHOP
  • Cocaine
  • Endoplasmic reticulum stress
  • Microglia

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Role of endoplasmic reticulum (ER) stress in cocaine-induced microglial cell death. / Costa, Blaise Mathias; Yao, Honghong; Yang, Lu; Buch, Shilpa J.

In: Journal of Neuroimmune Pharmacology, Vol. 8, No. 3, 01.06.2013, p. 705-714.

Research output: Contribution to journalArticle

Costa, Blaise Mathias ; Yao, Honghong ; Yang, Lu ; Buch, Shilpa J. / Role of endoplasmic reticulum (ER) stress in cocaine-induced microglial cell death. In: Journal of Neuroimmune Pharmacology. 2013 ; Vol. 8, No. 3. pp. 705-714.
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