Related Experiment Video
Updated: Jul 4, 2025
06:53
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
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The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway
Paul Bigliardi1,2, Seetanshu Junnarkar3, Chinmay Markale1,2
1Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA.
Cells
|February 9, 2024
Summary
Delta-opioid receptor (DOPr) activation delays PER2 gene expression by shifting circadian rhythms. This mechanism, involving beta-arrestin-1 and chromatin remodeling, may link skin wound healing to cancer development.
Area of Science:
- Dermatology
- Chronobiology
- Molecular Biology
Background:
- Circadian rhythmicity influences skin homeostasis, regeneration, and aging.
- The PER2 circadian clock gene is a vital antitumor gene.
- Delta-opioid receptors (DOPrs) are crucial for skin cell functions and cancer development.
Purpose of the Study:
- To investigate the association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity.
- To elucidate the molecular mechanisms linking DOPr activation to circadian gene expression in skin cells.
Main Methods:
- Conducted a 48-hour circadian rhythm experiment with RNA sampling every 5 hours.
- Utilized N/TERT-1 keratinocytes synchronized by dexamethasone.
- Employed confocal microscopy and ChIP assays to analyze protein-DNA interactions and gene expression.
Main Results:
- DOPr activation by Met-Enkephalin caused a significant 5.6-hour delay in PER2 gene expression.
- DOPr activation led to nuclear localization of the DOPr-β-arrestin-1 complex.
- β-arrestin-1 binding to the PER2 promoter was phase-shifted and enhanced by DOPr activation, involving histone-4 acetylation.
Conclusions:
- DOPr activation induces a phase shift in PER2 expression through β-arrestin-1-mediated chromatin remodeling.
- This pathway suggests a role for DOPr in cancer development, mirroring its function in wound healing.
- Findings highlight the interplay between opioid signaling and circadian clock genes in skin biology and disease.
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