Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene Per1
DOI:
https://doi.org/10.1186/1740-3391-9-6Keywords:
Food-entrainable oscillator, liver explants, clock proteins, intracellular calcium, SERCA, IP3R, RyRAbstract
Background: The role played by calcium as a regulator of circadian rhythms is not well understood. The effect of the pharmacological inhibition of the ryanodine receptor (RyR), inositol 1,4,5-trisphosphate receptor (IP3R), and endoplasmic-reticulum Ca2+-ATPase (SERCA), as well as the intracellular Ca2+-chelator BAPTA-AM was explored on the 24-h rhythmicity of the liver-clock protein PER1 in an experimental model of circadian synchronization by light and restricted-feeding schedules.
Methods: Liver explants from Period1-luciferase (Per1-luc) transgenic rats with either free food access or with a restricted meal schedule were treated for several days with drugs to inhibit the activity of IP3Rs (2-APB), RyRs (ryanodine), or SERCA (thapsigargin) as well as to suppress intracellular calcium fluctuations (BAPTA-AM). The period of Per1-luc expression was measured during and after drug administration.
Results: Liver explants from rats fed ad libitum showed a lengthened period in response to all the drugs tested. The pharmacological treatments of the explants from meal-entrained rats induced the same pattern, with the exception of the ryanodine treatment which, unexpectedly, did not modify the Per1-luc period. All effects associated with drug application were reversed after washout, indicating that none of the pharmacological treatments was toxic to the liver cultures.
Conclusions: Our data suggest that Ca2+ mobilized from internal deposits modulates the molecular circadian clock in the liver of rats entrained by light and by restricted meal access.
Published
Issue
Section
License
Copyright (c) 2011 The Author(s)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms. If a submission is rejected or withdrawn prior to publication, all rights return to the author(s):
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
Submitting to the journal implicitly confirms that all named authors and rights holders have agreed to the above terms of publication. It is the submitting author's responsibility to ensure all authors and relevant institutional bodies have given their agreement at the point of submission.
Note: some institutions require authors to seek written approval in relation to the terms of publication. Should this be required, authors can request a separate licence agreement document from the editorial team (e.g. authors who are Crown employees).