Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.
Journal Article (Journal Article)
OBJECTIVE: We previously examined the expression of specific C-terminal μ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ± HIV encephalitis (HIVE). In the present study, we examined the N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling. METHODS AND RESULTS: We found segregation of expression ranging from undetectable to seemingly exclusive across nervous system cell types compared to the pool of C-terminal MOR splice variants using the real-time polymerase chain reaction (RT-PCR). Expression of MOR-1K mRNA was also increased in HIV-infected individuals with combined neurocognitive impairment and HIVE compared with the other groups. MOR-1K expression correlated with the level of patient neurocognitive impairment, whereas the pool of C-terminal MOR splice variants did not. HIVE was also associated with increased expression of the inflammatory mediators MCP-1, MCP-2, and RANTES, but not the host HIV coreceptors CXCR4 and CCR5 or the CD4 receptor using qRT-PCR. Network analysis of microarray data from these same patients revealed filamin A (FLNA) as a possible interaction partner with MOR-1K, and FLNA gene expression was also found to be upregulated in HIVE using qRT-PCR. Overexpression of FLNA in HEK293 cells redistributed MOR-1K from intracellular compartments to the cell surface. CONCLUSION: These results suggest that HIVE, and neurocognitive impairment depending on its severity, are associated with enhanced MOR-1K signaling through both increased expression and trafficking to the cell surface, which may alter the contribution of MOR receptor isoforms and exacerbate the effects of MOR activation in neuroAIDS.
- Dever, SM; Costin, BN; Xu, R; El-Hage, N; Balinang, J; Samoshkin, A; O'Brien, MA; McRae, M; Diatchenko, L; Knapp, PE; Hauser, KF
- January 2, 2014
Volume / Issue
- 28 / 1
Start / End Page
- 19 - 30
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)