PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

Xuhui Zhu, Honghong Yao, Fuwang Peng, Shannon Callen, Shilpa J Buch

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, thereby underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.

Original languageEnglish (US)
Pages (from-to)286-291
Number of pages6
JournalToxicology and Applied Pharmacology
Volume240
Issue number2
DOIs
StatePublished - Oct 15 2009

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Calcium Signaling
Cytoprotection
Egtazic Acid
Toxicity
HIV-1
Glutamic Acid
HIV
AIDS Dementia Complex
Human Immunodeficiency Virus Proteins
Calcium
Critical Pathways
Poisons
N-Methylaspartate
tat Gene Products
Phosphorylation
Apoptosis
Viruses
Brain
Chemical activation
Neuroprotection

Keywords

  • Erk
  • Glutamate Ca
  • PDGF
  • SH-SY5Y cells

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium. / Zhu, Xuhui; Yao, Honghong; Peng, Fuwang; Callen, Shannon; Buch, Shilpa J.

In: Toxicology and Applied Pharmacology, Vol. 240, No. 2, 15.10.2009, p. 286-291.

Research output: Contribution to journalArticle

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