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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 182-191 |
| Number of pages | 10 |
| Journal | Journal of NeuroImmune Pharmacology |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 1 2016 |
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Keywords
- gp120
- HIV-1
- NMDA receptor
- Phosphorylation
- Synapse
ASJC Scopus subject areas
- Pharmacology
- Immunology and Allergy
- Immunology
- Neuroscience (miscellaneous)
Cite this
HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors. / Ru, Wenjuan; Tang, Shao-Jun.
In: Journal of NeuroImmune Pharmacology, Vol. 11, No. 1, 01.03.2016, p. 182-191.Research output: Contribution to journal › Article
}
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
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 - gp120
KW - HIV-1
KW - NMDA receptor
KW - Phosphorylation
KW - Synapse
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
VL - 11
SP - 182
EP - 191
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
SN - 1557-1890
IS - 1
ER -