Epigenetic control of the expression of opioid receptor genes

Li, Wei

doi:10.4161/epi.3.3.6296

Cited by 20 publications

(16 citation statements)

References 12 publications

(13 reference statements)

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“…Reduced gene expression is observed in this population, possibly as a result of reduced binding affinity for transcription factors, although increased binding of transcription factors via opioid-mediated activation of the cAMP-PKA pathway has also been observed (Wei, 2008; Xu and Carr, 2001a; Xu and Carr, 2001b). Whether this translates to differences in the utilization of the proximal, distal, and exon 11 promoters, and in the subsequent availability of different pre-mRNA transcripts for alternative splicing events, remains unclear.…”

Section: Regulatory Mechanisms Of Opioid Receptor Splicing Specificitymentioning

confidence: 87%

“…Multiple mechanisms have been suggested to explain spatial and temporal regulation of opioid receptor expression as well as for pharmacological data that suggests the existence of additional opioid receptor subtypes. Epigenetic mechanisms represent a major factor through which opioid gene expression is regulated (Regan et al, 2011; Wei, 2008; Wei and Loh, 2002). Likewise, short nucleotide polymorphisms (SNPs) of opioid receptor genes have been found to alter opioid pharmacology (Levran et al, 2012; Pasternak and Pan, 2013; Shabalina et al, 2009; Shi et al, 2002).…”

Section: Alternative Splicing Of Opioid Receptorsmentioning

confidence: 99%

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Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

2015

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Despite the identification and characterization of four opioid receptor subtypes and the genes from which they are encoded, pharmacological data does not conform to the predications of a four opioid receptor model. Instead, current studies of opioid pharmacology suggest the existence of additional receptor subtypes; however, no additional opioid receptor subtype has been identified to date. It is now understood that this discrepancy is due to the generation of multiple isoforms of opioid receptor subtypes. While several mechanisms are utilized to generate these isoforms, the primary mechanism involves alternative splicing of the pre-mRNA transcript. Extensive alternative splicing patterns for opioid receptors have since been identified and discrepancies in opioid pharmacology are now partially attributed to variable expression of these isoforms. Recent studies have been successful in characterizing the localization of these isoforms as well as their specificity in ligand binding; however, the regulation of opioid receptor splicing specificity is poorly characterized. Furthermore, the functional significance of individual receptor isoforms and the extent to which opioid- and/or HIV-mediated changes in the opioid receptor isoform profile contributes to altered opioid pharmacology or the well-known physiological role of opioids in the exacerbation of HIV neurocognitive dysfunction is unknown. As such, the current review details constitutive splicing mechanisms as well as the specific architecture of opioid receptor genes, transcripts, and receptors in order to highlight the current understanding of opioid receptor isoforms, potential mechanisms of their regulation and signaling, and their functional significance in both opioid pharmacology and HIV-associated neuropathology.

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Section: Regulatory Mechanisms Of Opioid Receptor Splicing Specificitymentioning

confidence: 87%

Section: Alternative Splicing Of Opioid Receptorsmentioning

confidence: 99%

Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

2015

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“…Incubation of the preinduced BMSCs with RA was reported to modulate and increase the expression of growth factors and neurotrophins (Ghorbanian et al, 2009, Fisher and Lakshmanan, 1990, Hernández-Pedro et a., 2008, Wei, 2008. In fact, RA is present in various tissues of both embryonic and adult animals, in particular in the nervous system (Wagner et al, 1992), where it promotes neuronal differentiation (Takahashi et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

In vitro differentiation of GABAergic cells from bone marrow stromal cells using Potassium Chloride as inducer

Gharibani

Tiraihi

Arabkheradmand

2010

Restorative Neurology and Neuroscience

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Bone marrow stromal cells (BMSCs) are multipotent and can be induced to differentiate into different lineages including osteogenic, chondrogenic, myogenic and neuronal phenotypes. BMSCs were reported to be a suitable option for regenerative medical research. In this study, BMSCs were induced into GABAergic phenotypes using β-mercaptoethanol (βME) and retinoic acid (RA) as preinducers followed by potassium chloride as inducer, and were evaluated by fibronectin and Oct-4. The percentages of cells immunoreactive for nestin, neurofilaments (NF 68, NF 160, and NF 200), GABA and GABA synthesizing and packaging enzymes (GAD1, GAD2, VGAT) were used for evaluating GABAergic differentiation. RT-PCR was used for confirming the expression of these enzymes. The differentiated cells were loaded and unloaded with FM1-43 in order to assess the functionality of the cells. At the preinduction stage, the cells downregulated fibronectin and Oct-4, and expressed neuronal markers. At the induction stage, the preinduced cells transdifferentiated into GABAergic cells, as confirmed by immunohistochemistry and RT-PCR. The GABAergic cells were stained and destained with FM1-43. Therefore, the two-stage induction protocol resulted in transdifferentiation of BMSCs into GABAergic cells with synaptic release upon stimulation.

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“…During neuronal differentiation there is a shift in this expression, with the KOR and DOR encoding genes being silenced and a robust activation of OPRM1 . This is followed by a reactivation of the KOR and DOR genes (Wei, 2008).…”

Section: Epigenetic Regulation Of Oprm1 Expressionmentioning

confidence: 99%

Epigenetics of µ‐opioid receptors: Intersection with HIV‐1 infection of the central nervous system

Regan

Dave

Datta

et al. 2012

Journal Cellular Physiology

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The abuse of intravenous drugs, such as heroin, has become a major public health concern due to the increased risk of HIV-1 infection. Opioids such as heroin were originally identified and subsequently abused for their analgesic effects. However, many investigations have found additional effects of opioids, including regulation of the immune system. As such, chronic opioid abuse has been shown to promote HIV-1 pathogenesis and facilitate HIV-1-associated neurocognitive dysfunction. Clinical opioids, such as morphine and methadone, as well as illicit opioids, such as heroin, exert their effects primarily through interactions with the μ-opioid receptor (MOR). However, the mechanisms by which opioids enhance neurocognitive dysfunction through MOR-mediated signaling pathways are not completely understood. New findings in the regulation of MOR expression, particularly epigenetic and transcriptional regulation as well as alternative splicing, sheds new insights into possible mechanisms of HIV-1 and opiate synergy. In this review, we identify mechanisms regulating MOR expression and propose novel mechanisms by which opioids and HIV-1 may modulate this regulation. Additionally, we suggest that differential regulation of newly identified MOR isoforms by opioids and HIV-1 has functional consequence in enhancing HIV-1 neurocognitive dysfunction.

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Epigenetic control of the expression of opioid receptor genes

Cited by 20 publications

References 12 publications

Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

In vitro differentiation of GABAergic cells from bone marrow stromal cells using Potassium Chloride as inducer

Epigenetics of µ‐opioid receptors: Intersection with HIV‐1 infection of the central nervous system

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