The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway
The circadian rhythmicity of critical skin cell functions related to homeostasis, regeneration and aging has recently been highlighted. In this study, we suggest an important link between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. We find that activation of the Delta-opioid...
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| Format: | Thesis |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/104426 http://hdl.handle.net/10220/49501 |
| _version_ | 1811696685064126464 |
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| author | Junnarkar, Seetanshu Bharat |
| author2 | Tan Nguan Soon, Andrew |
| author_facet | Tan Nguan Soon, Andrew Junnarkar, Seetanshu Bharat |
| author_sort | Junnarkar, Seetanshu Bharat |
| collection | NTU |
| description | The circadian rhythmicity of critical skin cell functions related to homeostasis, regeneration and aging has recently been highlighted. In this study, we suggest an important link between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. We find that activation of the Delta-opioid receptor (DOPr) by its endogenous agonist Met-enkephalin in N/TERT-1 keratinocytes results in a phase shift in the expression of the core clock gene Per2 and in the nuclear localization of the DOPr - β-arrestin 1 complex. Furthermore, DOPr activation enhances and induces a phase shift in the rhythmic binding of β-arrestin1 to the Per2 promoter. Coupled with this finding, β-arrestin1 was found to regulate the transcription of its target genes, including Per2, by facilitating histone 4 acetylation. Taken together, we propose that activation of DOPr leads to a phase shift in Per2 expression via β-arrestin1 facilitated chromatin remodelling. We believe our results have potential implications in wound healing, DNA repair and chronopharmacology. |
| first_indexed | 2024-10-01T07:43:17Z |
| format | Thesis |
| id | ntu-10356/104426 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:43:17Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1044262023-02-28T18:47:36Z The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway Junnarkar, Seetanshu Bharat Tan Nguan Soon, Andrew School of Biological Sciences Institute of Medical Biology Science::Biological sciences The circadian rhythmicity of critical skin cell functions related to homeostasis, regeneration and aging has recently been highlighted. In this study, we suggest an important link between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. We find that activation of the Delta-opioid receptor (DOPr) by its endogenous agonist Met-enkephalin in N/TERT-1 keratinocytes results in a phase shift in the expression of the core clock gene Per2 and in the nuclear localization of the DOPr - β-arrestin 1 complex. Furthermore, DOPr activation enhances and induces a phase shift in the rhythmic binding of β-arrestin1 to the Per2 promoter. Coupled with this finding, β-arrestin1 was found to regulate the transcription of its target genes, including Per2, by facilitating histone 4 acetylation. Taken together, we propose that activation of DOPr leads to a phase shift in Per2 expression via β-arrestin1 facilitated chromatin remodelling. We believe our results have potential implications in wound healing, DNA repair and chronopharmacology. Doctor of Philosophy 2019-07-31T07:27:53Z 2019-12-06T21:32:31Z 2019-07-31T07:27:53Z 2019-12-06T21:32:31Z 2019 Thesis Junnarkar, S. B. (2019). The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/104426 http://hdl.handle.net/10220/49501 10.32657/10220/49501 en 141 p. application/pdf |
| spellingShingle | Science::Biological sciences Junnarkar, Seetanshu Bharat The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title | The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title_full | The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title_fullStr | The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title_full_unstemmed | The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title_short | The delta opioid receptor influences circadian rhythms in human N/TERT-1 keratinocytes through the β-arrestin pathway |
| title_sort | delta opioid receptor influences circadian rhythms in human n tert 1 keratinocytes through the β arrestin pathway |
| topic | Science::Biological sciences |
| url | https://hdl.handle.net/10356/104426 http://hdl.handle.net/10220/49501 |
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