PUBLICATION
Opioid and Notch signaling pathways are reciprocally regulated through miR- 29a and miR-212 expression
- Authors
- Garcia-Concejo, A., Jimenez-Gonzalez, A., Rodriguez, R.E.
- ID
- ZDB-PUB-180927-6
- Date
- 2018
- Source
- Biochimica et biophysica acta. General subjects 1862: 2605-2612 (Journal)
- Registered Authors
- Rodriguez, Raquel E.
- Keywords
- Addiction, Danio rerio, Morphine, Notch, microRNA, mu opioid receptor
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cyclic AMP Response Element-Binding Protein/metabolism
- Humans
- MicroRNAs/metabolism*
- NF-kappa B/metabolism
- Opioid Peptides/metabolism*
- Phosphorylation
- Protein Binding
- Receptor, Notch1/genetics
- Receptor, Notch1/metabolism*
- Signal Transduction/genetics*
- Zebrafish/embryology
- PubMed
- 30251655 Full text @ BBA General Subjects
Citation
Garcia-Concejo, A., Jimenez-Gonzalez, A., Rodriguez, R.E. (2018) Opioid and Notch signaling pathways are reciprocally regulated through miR- 29a and miR-212 expression. Biochimica et biophysica acta. General subjects. 1862:2605-2612.
Abstract
Background The abuse of opioids, such as morphine and phentanyl or other drugs as heroin is a social and health problem that affects an increasing number of people each year. The activation of the mu opioid receptor triggers several molecular changes that alter the expression of diverse genes, including miRNAs. The dysregulation of these molecules could explain some of the developmental alterations that are induced after drug intake. In addition, the Notch signaling cascade has also been related to alterations on these processes.
Methods Zebrafish embryos and SH-SY5Y cells were used to assess the effects of opioid and Notch signaling on the expression on miR-29a and miR-212/132 by qPCR and ChIP-qPCR. Notch1 expression was analyzed using in situ hybridization on 24 hpf zebrafish embryos. In addition, OPRM1 and NICD levels were measured using western blot on the cultured cells to determine the cross-talk between the two pathways.
Results We have observed changes in the levels of miR-212/132 after administrating DAPT to zebrafish embryos indicating that this pathway could be regulating mu opioid receptor expression. In addition, the ISH experiment showed changes in Notch1 expression after morphine and DAPT administration. Moreover, morphine affects the expression of miR-29a through NF-κB, therefore controlling the cleavage and activation of Notch through ADAM12 expression.
Conclusions This study shows that these two pathways are closely related, and could explain the alterations triggered in the early stages of the development of addiction.
General significance Opioid and Notch pathway are reciprocally regulated by the miRNAs 212/132 and 29a.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping