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

Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Research Abstract Details 

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Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Abstract Text:

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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Platelet-derived growth factor protects neurons against gp120-mediated toxicity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of neurovirology

VOLUME: 14

Page Numbers: 62-72

Journal Abbreviation: J. Neurovirol.

ISSN: 1538-2443

DAY: 26

MONTH: Jan

YEAR: 2008

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

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LANGUAGE: eng

NlmUniqueID: 9508123

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Grant and Affiliation Information for Platelet-derived growth factor protects neurons against gp120-mediated toxicity.

AFFILIATION: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR016443

ACRONYM: RR

MEDLINETA: J Neurovirol

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