TY - JOUR
T1 - HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors
AU - Ru, Wenjuan
AU - Tang, Shao Jun
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - HIV-1
KW - NMDA receptor
KW - Phosphorylation
KW - Synapse
KW - gp120
UR - http://www.scopus.com/inward/record.url?scp=84957433796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957433796&partnerID=8YFLogxK
U2 - 10.1007/s11481-015-9644-7
DO - 10.1007/s11481-015-9644-7
M3 - Article
C2 - 26582091
AN - SCOPUS:84957433796
SN - 1557-1890
VL - 11
SP - 182
EP - 191
JO - Journal of Neuroimmune Pharmacology
JF - Journal of Neuroimmune Pharmacology
IS - 1
ER -