Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway

Research output: Contribution to journalJournal articlepeer-review

Standard

Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway. / Small, Lewin; Altıntaş, Ali; Laker, Rhianna C; Ehrlich, Amy; Pattamaprapanont, Pattarawan; Villarroel, Julia; Pillon, Nicolas J; Zierath, Juleen R; Barrès, Romain.

In: The Journal of Physiology, Vol. 598, No. 24, 2020, p. 5739-5752.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Small, L, Altıntaş, A, Laker, RC, Ehrlich, A, Pattamaprapanont, P, Villarroel, J, Pillon, NJ, Zierath, JR & Barrès, R 2020, 'Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway', The Journal of Physiology, vol. 598, no. 24, pp. 5739-5752. https://doi.org/10.1113/JP280428

APA

Small, L., Altıntaş, A., Laker, R. C., Ehrlich, A., Pattamaprapanont, P., Villarroel, J., Pillon, N. J., Zierath, J. R., & Barrès, R. (2020). Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway. The Journal of Physiology, 598(24), 5739-5752. https://doi.org/10.1113/JP280428

Vancouver

Small L, Altıntaş A, Laker RC, Ehrlich A, Pattamaprapanont P, Villarroel J et al. Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway. The Journal of Physiology. 2020;598(24):5739-5752. https://doi.org/10.1113/JP280428

Author

Small, Lewin ; Altıntaş, Ali ; Laker, Rhianna C ; Ehrlich, Amy ; Pattamaprapanont, Pattarawan ; Villarroel, Julia ; Pillon, Nicolas J ; Zierath, Juleen R ; Barrès, Romain. / Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway. In: The Journal of Physiology. 2020 ; Vol. 598, No. 24. pp. 5739-5752.

Bibtex

@article{3707838614034003b545c9ba1bb17445,
title = "Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway",
abstract = "KEY POINTS: Exercising at different times of day elicits different effects on exercise performance and metabolic health however, the specific signals driving the observed time-of-day specific effects of exercise are not fully identified; Exercise influences the skeletal muscle circadian clock, but the relative contribution of muscle contraction and extracellular signals is unknown; Here we show that contraction acutely increases the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifts Per2 rhythmicity in muscle cells. This contraction effect on core clock genes is mediated through a calcium-dependant mechanism; Our results suggest that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by muscle contraction. Contraction interventions may be used to mimic some time-of-day specific effects of exercise on metabolism and muscle performance.ABSTRACT: Exercise entrains the central and peripheral circadian clocks, however, the mechanism by which exercise modulates expression of skeletal muscle clock genes is unclear. Here, our aim was to determine if skeletal muscle contraction alone could directly influence circadian rhythmicity and uncover the underlying mechanism by which contraction modulates clock gene expression. We investigated the expression of core clock genes in human skeletal muscle after acute exercise, as well as following in vitro contraction in mouse soleus muscle and cultured C2C12 skeletal muscle myotubes. Additionally, we interrogated the molecular pathways by which skeletal muscle contraction could influence clock gene expression. Contraction acutely increased the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifted Per2 rhythmicity in C2C12 myotubes in vitro. Further investigation revealed that pharmacologically increasing cytosolic calcium concentrations by ionomycin treatment mimicked the effect of contraction on Per2 expression. Similarly, treatment with the calcium channel blocker, nifedipine, blocked the effect of electric pulse stimulation (EPS) induced contraction on Per2 expression. Increased calcium influx from contraction lead to binding of the phosphorylated form of cAMP response element-binding protein (CREB) to the Per2 promoter, suggesting a role of CREB in contraction-induced Per2 transcription. Thus, by dissociating the effect of muscle contraction alone from the whole effect of exercise, our investigations indicate that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by contraction. This article is protected by copyright. All rights reserved.",
author = "Lewin Small and Ali Altınta{\c s} and Laker, {Rhianna C} and Amy Ehrlich and Pattarawan Pattamaprapanont and Julia Villarroel and Pillon, {Nicolas J} and Zierath, {Juleen R} and Romain Barr{\`e}s",
year = "2020",
doi = "10.1113/JP280428",
language = "English",
volume = "598",
pages = "5739--5752",
journal = "The Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "24",

}

RIS

TY - JOUR

T1 - Contraction influences Per2 gene expression in skeletal muscle through a calcium-dependent pathway

AU - Small, Lewin

AU - Altıntaş, Ali

AU - Laker, Rhianna C

AU - Ehrlich, Amy

AU - Pattamaprapanont, Pattarawan

AU - Villarroel, Julia

AU - Pillon, Nicolas J

AU - Zierath, Juleen R

AU - Barrès, Romain

PY - 2020

Y1 - 2020

N2 - KEY POINTS: Exercising at different times of day elicits different effects on exercise performance and metabolic health however, the specific signals driving the observed time-of-day specific effects of exercise are not fully identified; Exercise influences the skeletal muscle circadian clock, but the relative contribution of muscle contraction and extracellular signals is unknown; Here we show that contraction acutely increases the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifts Per2 rhythmicity in muscle cells. This contraction effect on core clock genes is mediated through a calcium-dependant mechanism; Our results suggest that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by muscle contraction. Contraction interventions may be used to mimic some time-of-day specific effects of exercise on metabolism and muscle performance.ABSTRACT: Exercise entrains the central and peripheral circadian clocks, however, the mechanism by which exercise modulates expression of skeletal muscle clock genes is unclear. Here, our aim was to determine if skeletal muscle contraction alone could directly influence circadian rhythmicity and uncover the underlying mechanism by which contraction modulates clock gene expression. We investigated the expression of core clock genes in human skeletal muscle after acute exercise, as well as following in vitro contraction in mouse soleus muscle and cultured C2C12 skeletal muscle myotubes. Additionally, we interrogated the molecular pathways by which skeletal muscle contraction could influence clock gene expression. Contraction acutely increased the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifted Per2 rhythmicity in C2C12 myotubes in vitro. Further investigation revealed that pharmacologically increasing cytosolic calcium concentrations by ionomycin treatment mimicked the effect of contraction on Per2 expression. Similarly, treatment with the calcium channel blocker, nifedipine, blocked the effect of electric pulse stimulation (EPS) induced contraction on Per2 expression. Increased calcium influx from contraction lead to binding of the phosphorylated form of cAMP response element-binding protein (CREB) to the Per2 promoter, suggesting a role of CREB in contraction-induced Per2 transcription. Thus, by dissociating the effect of muscle contraction alone from the whole effect of exercise, our investigations indicate that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by contraction. This article is protected by copyright. All rights reserved.

AB - KEY POINTS: Exercising at different times of day elicits different effects on exercise performance and metabolic health however, the specific signals driving the observed time-of-day specific effects of exercise are not fully identified; Exercise influences the skeletal muscle circadian clock, but the relative contribution of muscle contraction and extracellular signals is unknown; Here we show that contraction acutely increases the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifts Per2 rhythmicity in muscle cells. This contraction effect on core clock genes is mediated through a calcium-dependant mechanism; Our results suggest that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by muscle contraction. Contraction interventions may be used to mimic some time-of-day specific effects of exercise on metabolism and muscle performance.ABSTRACT: Exercise entrains the central and peripheral circadian clocks, however, the mechanism by which exercise modulates expression of skeletal muscle clock genes is unclear. Here, our aim was to determine if skeletal muscle contraction alone could directly influence circadian rhythmicity and uncover the underlying mechanism by which contraction modulates clock gene expression. We investigated the expression of core clock genes in human skeletal muscle after acute exercise, as well as following in vitro contraction in mouse soleus muscle and cultured C2C12 skeletal muscle myotubes. Additionally, we interrogated the molecular pathways by which skeletal muscle contraction could influence clock gene expression. Contraction acutely increased the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase-shifted Per2 rhythmicity in C2C12 myotubes in vitro. Further investigation revealed that pharmacologically increasing cytosolic calcium concentrations by ionomycin treatment mimicked the effect of contraction on Per2 expression. Similarly, treatment with the calcium channel blocker, nifedipine, blocked the effect of electric pulse stimulation (EPS) induced contraction on Per2 expression. Increased calcium influx from contraction lead to binding of the phosphorylated form of cAMP response element-binding protein (CREB) to the Per2 promoter, suggesting a role of CREB in contraction-induced Per2 transcription. Thus, by dissociating the effect of muscle contraction alone from the whole effect of exercise, our investigations indicate that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by contraction. This article is protected by copyright. All rights reserved.

U2 - 10.1113/JP280428

DO - 10.1113/JP280428

M3 - Journal article

C2 - 32939754

VL - 598

SP - 5739

EP - 5752

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 24

ER -

ID: 249102462