Differential expression of the alternatively spliced OPRM1 isoform µ-opioid receptor-1K in HIV-infected individuals.
AIDS
; 28(1): 19-30, 2014 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-24413261
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 impairmentâ±âHIV encephalitis (HIVE). In the present study, we examined the N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling. METHODS ANDRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Splicing de RNA
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Complexo AIDS Demência
/
Receptores Opioides mu
Limite:
Humans
Idioma:
En
Revista:
AIDS
Ano de publicação:
2014
Tipo de documento:
Article