Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.
Title | Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Dever, SM, Costin, BN, Xu, R, El-Hage, N, Balinang, J, Samoshkin, A, O'Brien, MA, McRae, M, Diatchenko, L, Knapp, PE, Hauser, KF |
Journal | AIDS |
Volume | 28 |
Issue | 1 |
Pagination | 19-30 |
Date Published | 2014 Jan 02 |
ISSN | 1473-5571 |
Keywords | AIDS Dementia Complex, External, HIV Infections, Humans, Protein Isoforms, Real-Time Polymerase Chain Reaction, Receptors, Opioid, mu, RNA Splicing |
Abstract | 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. |
DOI | 10.1097/QAD.0000000000000113 |
Alternate Journal | AIDS |
PubMed ID | 24413261 |
PubMed Central ID | PMC3939043 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States U01 MH083507 / MH / NIMH NIH HHS / United States R24 MH059724 / MH / NIMH NIH HHS / United States K02 DA027374 / DA / NIDA NIH HHS / United States T90 DE021986 / DE / NIDCR NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States R24 MH59724 / MH / NIMH NIH HHS / United States 5R41 DA032293-02 / DA / NIDA NIH HHS / United States R24 NS045491 / NS / NINDS NIH HHS / United States T32 DA007027 / DA / NIDA NIH HHS / United States R01 DA018633 / DA / NIDA NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States F31 DA039803 / DA / NIDA NIH HHS / United States F32 DA033898 / DA / NIDA NIH HHS / United States R24 MH059745 / MH / NIMH NIH HHS / United States R24 NS038841 / NS / NINDS NIH HHS / United States 5U01 MH083500 / MH / NIMH NIH HHS / United States R24 NS45491 / NS / NINDS NIH HHS / United States N01 MH032002 / MH / NIMH NIH HHS / United States U01 MH083501 / MH / NIMH NIH HHS / United States R01 DA033200 / DA / NIDA NIH HHS / United States R01 DA034231 / DA / NIDA NIH HHS / United States R24 MH59745 / MH / NIMH NIH HHS / United States U01 MH083545 / MH / NIMH NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States R41 DA032293 / DA / NIDA NIH HHS / United States R01 DA024461 / DA / NIDA NIH HHS / United States 5T90 DE021986-02 / DE / NIDCR NIH HHS / United States NS38841 / NS / NINDS NIH HHS / United States |