@article{66946a3e0c0f4e88ae43b0a2e4256aa7,
title = "HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors",
abstract = "HIV-1 envelope glycoprotein gp120 (gp120) is a major virulence protein implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Although gp120 has been suggested to cause synaptic and neuronal injuries by disrupting NMDA receptor (NMDAR) function, the underlying mechanism is unclear. Here, we show that gp120Bal down-regulates the phosphorylation of the NMDAR subunit1 NR1 (at Ser896 and Ser897), which is essential for NMDAR function. This effect of gp120Bal is blocked by specific antagonists of both NMDA and AMPA receptors, indicating a critical role of synaptic activation. Furthermore, AMD3100 and maraviroc, antagonists of CCR5 and CXCR4 chemokine receptors, respectively, inhibit the effect of gp120Bal on NR1, suggesting that CXCR4 and CCR5 activation are involved. These findings may provide mechanistic insights into the synaptopathogenesis caused by HIV-1 infection.",
keywords = "HIV-1, NMDA receptor, Phosphorylation, Synapse, gp120",
author = "Wenjuan Ru and Tang, {Shao Jun}",
note = "Funding Information: HIV-1 coat protein gp120Bal (Cat # 4961) was obtained from the NIH AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH. The protein in PBS was aliquoted and stored at −80 °C until use. Gp120 protein with only a single freeze-thaw cycle was used. Maraviroc (Cat# 11,580, NIH AIDS Research and Reference Reagent Program) and D-APV (cat# 165,304; Calbiochem) were dissolved in ultrapure water. Bicyclam JM-2987 (AMD3100) (Cat#8128; NIH AIDS Research and Reference Reagent Program) and CNQX (Cat#C239; Sigma) were prepared in DMSO. Antibodies for immunoblotting were: anti-NR1 (1:2000; Cat # 06–311; Millipore), anti-phospho-NR1 (Ser896) (1:1000; Cat#06–640; Millipore), anti-phospho-NR1 (Ser897) (1:1000; Cat#ABN99; Millipore), caspase-3 (1:1000; Cat#9662; Cell Signaling Technology) and anti-β-actin (1:1000; Cat # sc-1616-R; Santa Cruz Biotechnology) antibodies. Antibodies for immunofluorescence staining are: microtubule-associated protein-2 (MAP-2) (1:500; Cat#ab5392, Abcam), Cleaved Caspase-3 (Asp175) (5A1E) (1:200, Cat# 9661, Cell Signaling Technology). Funding Information: HIV-1 gp120, Maraviroc and AMD3100 were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH. This work was supported by NIH grants NS079166 and DA036165 to SJT. Publisher Copyright: {\textcopyright} 2015, Springer Science+Business Media New York.",
year = "2016",
month = mar,
day = "1",
doi = "10.1007/s11481-015-9644-7",
language = "English (US)",
volume = "11",
pages = "182--191",
journal = "Journal of NeuroImmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "1",
}