Platelet-derived growth factor protects neurons against gp120-mediated toxicity

Fuwang Peng, Navneet Dhillon, Shannon Callen, Honghong Yao, Sirosh Bokhari, Xuhui Zhu, Hicham H. Baydoun, Shilpa J. Buch

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 has been implicated in mediating neuronal apoptosis, a hallmark feature of HIV-associated dementia (HAD). Mitigation of the toxic effects of gp120 could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study the authors hypothesized that neurotrophic factor, such as platelet-derived growth factor (PDGF), could protect the neurons against gp120-mediated apoptosis. SH-SY5Y cells treated with gp120 exhibited increased cell death when measured by lactate dehydrogenase (LDH) and deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay, with concomitant loss of neurites and increased cell rounding. Pretreatment with PDGF-BB, however, reduced gp120-associated neurotoxicity and rescued the neurite outgrowth. Additionally, gp120-mediated activation of caspase-3 was also significantly reduced in cells pretreated with PDGF-BB. Antiapoptotic effects of PDGF-BB were also confirmed by monitoring levels of anti- and proapoptotic genes, Bcl-xL and Bax, respectively. Furthermore, PDGF-mediated protection against gp120 involved the phosphoinositide (PI) 3-kinase/Akt pathway. Taken together these findings lead us to suggest that PDGF-BB could be considered as a therapeutic agent that can mitigate gp120-mediated neurotoxicity in HAD.

Original languageEnglish (US)
Pages (from-to)62-72
Number of pages11
JournalJournal of neurovirology
Volume14
Issue number1
DOIs
StatePublished - Mar 2008

Keywords

  • Gp120
  • HIV dementia
  • Neurons
  • PDGF

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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    Peng, F., Dhillon, N., Callen, S., Yao, H., Bokhari, S., Zhu, X., Baydoun, H. H., & Buch, S. J. (2008). Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Journal of neurovirology, 14(1), 62-72. https://doi.org/10.1080/13550280701809084