Cocaine potentiates astrocyte toxicity mediated by human immunodeficiency virus (HIV-1) protein gp120

Yanjing Yang, Honghong Yao, Yaman Lu, Chao Wang, Shilpa J Buch

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

It is becoming widely accepted that psychoactive drugs, often abused by HIV-I infected individuals, can significantly alter the progression of neuropathological changes observed in HIV-associated neurodegenerative diseases (HAND). The underlying mechanisms mediating these effects however, remain poorly understood. In the current study, we explored whether the psychostimulant drug cocaine could exacerbate toxicity mediated by gp120 in rat primary astrocytes. Exposure to both cocaine and gp120 resulted in increased cell toxicity compared to cells treated with either factor alone. The combinatorial toxicity of cocaine and gp120 was accompanied by an increase in caspase-3 activation. In addition, increased apoptosis of astrocytes in the presence of both the agents was associated with a concomitant increase in the production of intracellular reactive oxygen species and loss of mitochondrial membrane potential. Signaling pathways including c-jun Nteminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK), and nuclear factor (NF-κB) were identified to be major players in cocaine and gp120-mediated apoptosis of astrocytes. Our results demonstrated that cocaine-mediated potentiation of gp120 toxicity involved regulation of oxidative stress, mitochondrial membrane potential and MAPK signaling pathways.

Original languageEnglish (US)
Article numbere13427
JournalPloS one
Volume5
Issue number10
DOIs
StatePublished - Nov 17 2010

Fingerprint

Human Immunodeficiency Virus Proteins
cocaine
astrocytes
Human immunodeficiency virus
Human immunodeficiency virus 1
Cocaine
Viruses
Astrocytes
Toxicity
HIV-1
toxicity
Mitochondrial Membrane Potential
Mitogen-Activated Protein Kinases
Proteins
mitogen-activated protein kinase
membrane potential
proteins
apoptosis
Neurodegenerative diseases
Apoptosis

ASJC Scopus subject areas

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

Cite this

Cocaine potentiates astrocyte toxicity mediated by human immunodeficiency virus (HIV-1) protein gp120. / Yang, Yanjing; Yao, Honghong; Lu, Yaman; Wang, Chao; Buch, Shilpa J.

In: PloS one, Vol. 5, No. 10, e13427, 17.11.2010.

Research output: Contribution to journalArticle

Yang, Yanjing ; Yao, Honghong ; Lu, Yaman ; Wang, Chao ; Buch, Shilpa J. / Cocaine potentiates astrocyte toxicity mediated by human immunodeficiency virus (HIV-1) protein gp120. In: PloS one. 2010 ; Vol. 5, No. 10.
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