Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 13, No. 5, 2014, pp. 683-688
Bioline Code: pr14097
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 13, No. 5, 2014, pp. 683-688
© Copyright 2014 - Tropical Journal of Pharmaceutical Research
Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit the Uninfected CD4+ T Cells Apoptosis Induced by HIV-1 Extracellular Nef|
An, Gui-Jie; Li, Xiu-Ying; Sun, Han-Xiao; Liu, Sha; Zhou, Jing-Guang; Ding, Qing; Wei, Pi-Jin & Zhang, Guang
Purpose: To evaluate the potential role and cellular mechanism of the CXCR4 antagonist (N15P) derived from the N-terminal of viral macrophage inflammatory protein-II (vMIP-II) on the apoptosis induced by HIV-1 extracellular nef protein in vitro.
Method: Peripheral blood mononuclear cells (PBMCs) and Jurkat cells were treated with HIV-1 nef protein alone or together with N15P at different doses and time points. The competitive binding effect of N15P against nef was assessed via radioligand binding assays. Apoptosis was evaluated via terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay. The level of nuclear FOXO3a and phospho-FOXO3a was assessed by Western blotting.
Results: The interaction of 125I-nef with Jurkat cells was inhibited by N15P in a dose-dependent manner, with IC50 value of 0.3516 ng/ml. N15P protect against nef protein-induced apoptosis in a time- and concentration- dependent manner. The proapoptotic effect of extracellular nef protein in cells was associated with FOXO3a pathway and the changes in intracellular processes were blocked by N15P in a dose-dependent manner.
Conclusion: N15P inhibits the apoptosis of uninfected CD4+ T lymphocytes induced by HIV-1 extracellular nef protein. Therefore, N15P is a potential effective CXCR4 antagonist in the course of HIV and could prevent or delay the onset of AIDS.
HIV-1; Nef; vMIP-II; Bystander lymphocytes; Apoptosis; FOXO3a; CXCR4 antagonist; Macrophage; Inflammation
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