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

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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.

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, 5000 Wahl Hall East, University of Kansas Medical Center, 3901 Rainbow Boulevard, 66160, Kansas City, KS, USA

    Fuwang Peng, Navneet Dhillon, Shannon Callen, Honghong Yao, Xuhui Zhu & Shilpa Buch

  2. Department of Microbiology, University of Kansas Medical Center, Kansas City, Kansas, USA

    Sirosh Bokhari & Hicham H. Baydoun

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  1. Fuwang Peng
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  2. Navneet Dhillon
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  3. Shannon Callen
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  4. Honghong Yao
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  5. Sirosh Bokhari
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  6. Xuhui Zhu
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  7. Hicham H. Baydoun
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  8. Shilpa Buch
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Correspondence to Shilpa Buch.

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This work was supported by grants DA020392-01, MH62969-01, RR016443, MH-068212, and MH072355 from the National Institutes of Health.

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Peng, F., Dhillon, N., Callen, S. et al. Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Journal of NeuroVirology 14, 62–72 (2008). https://doi.org/10.1080/13550280701809084

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