Modulation of OPRM1 Alternative Splicing by Morphine and HIV-1 Nef.
Alternative splicing
Dependence
HIV
MOR–1
MOR–1X
Nef
OPRM1
Opioids
Journal
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
ISSN: 1557-1904
Titre abrégé: J Neuroimmune Pharmacol
Pays: United States
ID NLM: 101256586
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
21
01
2021
accepted:
06
08
2021
pubmed:
23
8
2021
medline:
15
12
2022
entrez:
22
8
2021
Statut:
ppublish
Résumé
Clinically used opioids, such as morphine, activate the mu opioid receptor (MOR) encoded by Opioid Receptor Mu 1 (OPRM1) gene. Examination of the opioid receptor genes showed that the human OPRM1 pre-mRNA undergoes extensive alternative splicing events and capable of expressing 21 isoforms. However, characterization of OPRM1 signaling is generalized, and only one isoform (MOR-1) has been extensively studied. Compounding this issue is the increasing significance of intravenous drug abuse in HIV neuropathogenesis. Here, we investigated the molecular impact of morphine and HIV-1 on regulation of OPRM1 pre-mRNA splicing in in vitro and in vivo models. Our results suggested that morphine treatment specifically induces the alternative splicing of MOR-1X isoform among the other isoforms analyzed in neuronal cells. Interestingly, alternative splicing and expression of MOR-1X isoform was also induced in postmortem brain tissues obtained from people with HIV (PWH). Additionally, treatment of control rats with morphine induced alternative splicing of MOR-1X in the brain regions involved in the reward pathways. More interestingly, HIV-1 transgenic (HIV-1Tg) rats, showed an additive induction of MOR-1X isoform with the exposure to morphine. To further assess the possible role of HIV secretory proteins in alternative splicing of OPRM1 gene, we analyzed the impact of HIV-1 Tat, gp120 and Nef proteins on alternative splicing of MOR-1X isoform. While the Tat and gp120 had no visible effects, treatment of neurons with Nef induced MOR-1X alternative splicing that was comparable to treatment with morphine. Altogether, our results suggest that HIV-1 may alter MOR isoform expression with Nef protein by amplifying the rate of MOR-1X alternative splicing induced by morphine.
Identifiants
pubmed: 34420144
doi: 10.1007/s11481-021-10009-4
pii: 10.1007/s11481-021-10009-4
pmc: PMC8859008
mid: NIHMS1751657
doi:
Substances chimiques
Morphine
76I7G6D29C
RNA Precursors
0
Protein Isoforms
0
Receptors, Opioid
0
OPRM1 protein, human
0
Receptors, Opioid, mu
0
nef protein, Human immunodeficiency virus 2
0
nef Gene Products, Human Immunodeficiency Virus
0
nef protein, Human immunodeficiency virus 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-288Subventions
Organisme : NIMH NIH HHS
ID : P30 MH092177
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA052284
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA043448
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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