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Differential expression of the alternatively spliced OPRM1 isoform ?-opioid receptor-1K in HIV-infected individuals.


ABSTRACT: We previously examined the expression of specific C-terminal ?-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.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.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.

SUBMITTER: Dever SM 

PROVIDER: S-EPMC3939043 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.

Dever Seth M SM   Costin Blair N BN   Xu Ruqiang R   El-Hage Nazira N   Balinang Joyce J   Samoshkin Alexander A   O'Brien Megan A MA   McRae Marypeace M   Diatchenko Luda L   Knapp Pamela E PE   Hauser Kurt F KF  

AIDS (London, England) 20140101 1


<h4>Objective</h4>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.<h4>Methods and results</h4>We found segregation of expression ranging from undetectable to seemingly exclusive acro  ...[more]

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