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Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene Per1.

Báez-Ruiz A, Díaz-Muñoz M - J Circadian Rhythms (2011)

Bottom Line: 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.The period of Per1-luc expression was measured during and after drug administration.All effects associated with drug application were reversed after washout, indicating that none of the pharmacological treatments was toxic to the liver cultures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departament de Neurobiología Moleculary Celular, Instituto de Neurobiología, UNAM-Juriquilla, Boulevard Juriquilla #3001, Apdo, Postal 1-1141, Querétaro, QRO, 76230, México. mdiaz@comunidad.unam.mx.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Representative double-plotted actograms of locomotor activity from Per1-luc transgenic rats fed ad-libitum or under restricted feeding in a 12:12 h light:dark cycle. In the first 5 days all rats were allowed free access to food; one group continued this condition from day 6 to day 15 (A) while another group (B) had a restricted feeding schedule with food available from ZT4 to ZT6 (indicated by the hatched box at the top of the figure inside the bar indicating the L:D cycle). These data are representative of 6 animals.
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Figure 1: Representative double-plotted actograms of locomotor activity from Per1-luc transgenic rats fed ad-libitum or under restricted feeding in a 12:12 h light:dark cycle. In the first 5 days all rats were allowed free access to food; one group continued this condition from day 6 to day 15 (A) while another group (B) had a restricted feeding schedule with food available from ZT4 to ZT6 (indicated by the hatched box at the top of the figure inside the bar indicating the L:D cycle). These data are representative of 6 animals.

Mentions: As expected, representative actograms of locomotor activity revealed the appearance of robust food anticipatory activity (FAA) when rats had access to a 2-h restricted meal for 10 days beginning on day 3 (Figure 1B). These data agree with previous reports and are accepted as evidence of FEO activation in Per1-luc transgenic rats [29].


Chronic inhibition of endoplasmic reticulum calcium-release channels and calcium-ATPase lengthens the period of hepatic clock gene Per1.

Báez-Ruiz A, Díaz-Muñoz M - J Circadian Rhythms (2011)

Representative double-plotted actograms of locomotor activity from Per1-luc transgenic rats fed ad-libitum or under restricted feeding in a 12:12 h light:dark cycle. In the first 5 days all rats were allowed free access to food; one group continued this condition from day 6 to day 15 (A) while another group (B) had a restricted feeding schedule with food available from ZT4 to ZT6 (indicated by the hatched box at the top of the figure inside the bar indicating the L:D cycle). These data are representative of 6 animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3142245&req=5

Figure 1: Representative double-plotted actograms of locomotor activity from Per1-luc transgenic rats fed ad-libitum or under restricted feeding in a 12:12 h light:dark cycle. In the first 5 days all rats were allowed free access to food; one group continued this condition from day 6 to day 15 (A) while another group (B) had a restricted feeding schedule with food available from ZT4 to ZT6 (indicated by the hatched box at the top of the figure inside the bar indicating the L:D cycle). These data are representative of 6 animals.
Mentions: As expected, representative actograms of locomotor activity revealed the appearance of robust food anticipatory activity (FAA) when rats had access to a 2-h restricted meal for 10 days beginning on day 3 (Figure 1B). These data agree with previous reports and are accepted as evidence of FEO activation in Per1-luc transgenic rats [29].

Bottom Line: 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.The period of Per1-luc expression was measured during and after drug administration.All effects associated with drug application were reversed after washout, indicating that none of the pharmacological treatments was toxic to the liver cultures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departament de Neurobiología Moleculary Celular, Instituto de Neurobiología, UNAM-Juriquilla, Boulevard Juriquilla #3001, Apdo, Postal 1-1141, Querétaro, QRO, 76230, México. mdiaz@comunidad.unam.mx.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus