Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>

<p>Abstract</p> <p>Background</p> <p>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 (IP<sub>3</sub>R),...

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Main Authors: Díaz-Muñoz Mauricio, Báez-Ruiz Adrián
Format: Article
Language:English
Published: Ubiquity Press 2011-07-01
Series:Journal of Circadian Rhythms
Subjects:
Online Access:http://www.jcircadianrhythms.com/content/9/1/6
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author Díaz-Muñoz Mauricio
Báez-Ruiz Adrián
author_facet Díaz-Muñoz Mauricio
Báez-Ruiz Adrián
author_sort Díaz-Muñoz Mauricio
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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 (IP<sub>3</sub>R), and endoplasmic-reticulum Ca<sup>2+</sup>-ATPase (SERCA), as well as the intracellular Ca<sup>2+</sup>-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.</p> <p>Methods</p> <p>Liver explants from <it>Period1-luciferase </it>(<it>Per1-luc</it>) 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 IP<sub>3</sub>Rs (2-APB), RyRs (ryanodine), or SERCA (thapsigargin) as well as to suppress intracellular calcium fluctuations (BAPTA-AM). The period of <it>Per1-luc </it>expression was measured during and after drug administration.</p> <p>Results</p> <p>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 <it>Per1-luc </it>period. All effects associated with drug application were reversed after washout, indicating that none of the pharmacological treatments was toxic to the liver cultures.</p> <p>Conclusions</p> <p>Our data suggest that Ca<sup>2+ </sup>mobilized from internal deposits modulates the molecular circadian clock in the liver of rats entrained by light and by restricted meal access.</p>
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spelling doaj.art-933b5c9d62bf4bd99e9c2830f6ef4ac72022-12-22T03:11:00ZengUbiquity PressJournal of Circadian Rhythms1740-33912011-07-0191610.1186/1740-3391-9-6Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>Díaz-Muñoz MauricioBáez-Ruiz Adrián<p>Abstract</p> <p>Background</p> <p>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 (IP<sub>3</sub>R), and endoplasmic-reticulum Ca<sup>2+</sup>-ATPase (SERCA), as well as the intracellular Ca<sup>2+</sup>-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.</p> <p>Methods</p> <p>Liver explants from <it>Period1-luciferase </it>(<it>Per1-luc</it>) 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 IP<sub>3</sub>Rs (2-APB), RyRs (ryanodine), or SERCA (thapsigargin) as well as to suppress intracellular calcium fluctuations (BAPTA-AM). The period of <it>Per1-luc </it>expression was measured during and after drug administration.</p> <p>Results</p> <p>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 <it>Per1-luc </it>period. All effects associated with drug application were reversed after washout, indicating that none of the pharmacological treatments was toxic to the liver cultures.</p> <p>Conclusions</p> <p>Our data suggest that Ca<sup>2+ </sup>mobilized from internal deposits modulates the molecular circadian clock in the liver of rats entrained by light and by restricted meal access.</p>http://www.jcircadianrhythms.com/content/9/1/6Food-entrainable oscillatorliver explantsclock proteinsintracellular calciumSERCAIP<sub>3</sub>RRyR.
spellingShingle Díaz-Muñoz Mauricio
Báez-Ruiz Adrián
Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
Journal of Circadian Rhythms
Food-entrainable oscillator
liver explants
clock proteins
intracellular calcium
SERCA
IP<sub>3</sub>R
RyR.
title Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
title_full Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
title_fullStr Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
title_full_unstemmed Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
title_short Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene <it>Per1</it>
title_sort chronic inhibition of endoplasmic reticulum calcium release channels and calcium atpase lengthens the period of hepatic clock gene it per1 it
topic Food-entrainable oscillator
liver explants
clock proteins
intracellular calcium
SERCA
IP<sub>3</sub>R
RyR.
url http://www.jcircadianrhythms.com/content/9/1/6
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