Acute Exercise Activates P38 MAPK and Increases the Expression of Telomere-protective Genes in Cardiac Muscle

Overview

Journal Exp Physiol

Specialty Physiology

Date 2017 Feb 7

PMID 28166612

Citations 24

Authors

Andrew T Ludlow

Laila Gratidao

Lindsay W Ludlow

Espen E Spangenburg

Stephen M Roth

Affiliations

Soon will be listed here.

Abstract

What is the central question of this study? A positive association between telomere length and exercise training has been shown in cardiac tissue of mice. It is currently unknown how each bout of exercise influences telomere-length-regulating proteins. We sought to determine how a bout of exercise altered the expression of telomere-length-regulating genes and a related signalling pathway in cardiac tissue of mice. What is the main finding and its importance? Acute exercise altered the expression of telomere-length-regulating genes in cardiac tissue and might be related to altered mitogen-activated protein kinase signalling. These findings are important in understanding how exercise provides a cardioprotective phenotype with ageing. Age is the greatest risk factor for cardiovascular disease. Telomere length is shorter in the hearts of aged mice compared with young mice, and short telomere length has been associated with an increased risk of cardiovascular disease. One year of voluntary wheel-running exercise attenuates the age-associated loss of telomere length and results in altered gene expression of telomere-length-maintaining and genome-stabilizing proteins in heart tissue of mice. Understanding the early adaptive response of the heart to an endurance exercise bout is paramount to understanding the impact of endurance exercise on heart tissue and cells. To this end, we studied mice before (BL), immediately after (TP1) and 1 h after a treadmill running bout (TP2). We measured the changes in expression of telomere-related genes (shelterin components), DNA-damage-sensing (p53 and Chk2) and DNA-repair genes (Ku70 and Ku80) and mitogen-activated protein kinase (MAPK) signalling. The TP1 animals had increased TRF1 and TRF2 protein and mRNA levels, greater expression of DNA-repair and -response genes (Chk2 and Ku80) and greater protein content of phosphorylated p38 MAPK compared with both BL and TP2 animals. These data provide insights into how physiological stressors remodel the heart tissue and how an early adaptive response mediated by exercise may be maintaining telomere length and/or stabilizing the heart genome through the upregulation of telomere-protective genes.

Citing Articles

The mechanism of NF-κB-TERT feedback regulation of granulosa cell apoptosis in PCOS rats.

Xue H, Hu Z, Liu S, Zhang S, Yang W, Li J PLoS One. 2024; 19(10):e0312115.

PMID: 39453929 PMC: 11508119. DOI: 10.1371/journal.pone.0312115.

Effect of aging and exercise on hTERT expression in thymus tissue of hTERT transgenic bacterial artificial chromosome mice.

Kim J, Ahn A, Ying J, Pollens-Voigt J, Ludlow A Geroscience. 2024; .

PMID: 39222198 DOI: 10.1007/s11357-024-01319-5.

The multifaceted benefits of walking for healthy aging: from Blue Zones to molecular mechanisms.

Ungvari Z, Fazekas-Pongor V, Csiszar A, Kunutsor S Geroscience. 2023; 45(6):3211-3239.

PMID: 37495893 PMC: 10643563. DOI: 10.1007/s11357-023-00873-8.

Exercise as a Therapy to Maintain Telomere Function and Prevent Cellular Senescence.

Kim J, Ahn A, Ying J, Hickman E, Ludlow A Exerc Sport Sci Rev. 2023; 51(4):150-160.

PMID: 37288975 PMC: 10526708. DOI: 10.1249/JES.0000000000000324.

The shelterin protein expansion of telomere dynamics: Linking early life adversity, life history, and the hallmarks of aging.

Wolf S, Shalev I Neurosci Biobehav Rev. 2023; 152:105261.

PMID: 37268182 PMC: 10527177. DOI: 10.1016/j.neubiorev.2023.105261.

References

Neufer P, Bamman M, Muoio D, Bouchard C, Cooper D, Goodpaster B . Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits. Cell Metab. 2015; 22(1):4-11. DOI: 10.1016/j.cmet.2015.05.011. View

Rose B, Force T, Wang Y . Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev. 2010; 90(4):1507-46. PMC: 3808831. DOI: 10.1152/physrev.00054.2009. View

Pfingsten J, Goodrich K, Taabazuing C, Ouenzar F, Chartrand P, Cech T . Mutually exclusive binding of telomerase RNA and DNA by Ku alters telomerase recruitment model. Cell. 2012; 148(5):922-32. PMC: 3327133. DOI: 10.1016/j.cell.2012.01.033. View

Laye M, Solomon T, Karstoft K, Pedersen K, Nielsen S, Pedersen B . Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event. J Appl Physiol (1985). 2011; 112(5):773-81. DOI: 10.1152/japplphysiol.00997.2011. View

de Lange T . How shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol. 2011; 75:167-77. DOI: 10.1101/sqb.2010.75.017. View

Armstrong L, Lako M, Lincoln J, Cairns P, Hole N . mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells. Mech Dev. 2000; 97(1-2):109-16. DOI: 10.1016/s0925-4773(00)00423-8. View

Shay J, Wright W . Hallmarks of telomeres in ageing research. J Pathol. 2007; 211(2):114-23. DOI: 10.1002/path.2090. View

OSullivan R, Karlseder J . Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol. 2010; 11(3):171-81. PMC: 2842081. DOI: 10.1038/nrm2848. View

Ludlow A, Roth S . Physical activity and telomere biology: exploring the link with aging-related disease prevention. J Aging Res. 2011; 2011:790378. PMC: 3043290. DOI: 10.4061/2011/790378. View

10.

Werner C, Hanhoun M, Widmann T, Kazakov A, Semenov A, Poss J . Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol. 2008; 52(6):470-82. DOI: 10.1016/j.jacc.2008.04.034. View

11.

van Berlo J, Molkentin J . An emerging consensus on cardiac regeneration. Nat Med. 2014; 20(12):1386-93. PMC: 4418535. DOI: 10.1038/nm.3764. View

12.

Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S . Dynamics of Cell Generation and Turnover in the Human Heart. Cell. 2015; 161(7):1566-75. DOI: 10.1016/j.cell.2015.05.026. View

13.

Dominguez L, Galioto A, Ferlisi A, Pineo A, Putignano E, Belvedere M . Ageing, lifestyle modifications, and cardiovascular disease in developing countries. J Nutr Health Aging. 2006; 10(2):143-9. View

14.

Spallarossa P, Altieri P, Aloi C, Garibaldi S, Barisione C, Ghigliotti G . Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2. Am J Physiol Heart Circ Physiol. 2009; 297(6):H2169-81. DOI: 10.1152/ajpheart.00068.2009. View

15.

Ludlow A, Zimmerman J, Witkowski S, Hearn J, Hatfield B, Roth S . Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc. 2008; 40(10):1764-71. PMC: 2581416. DOI: 10.1249/MSS.0b013e31817c92aa. View

16.

Blackburn E, Epel E, Lin J . Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science. 2016; 350(6265):1193-8. DOI: 10.1126/science.aab3389. View

17.

Collado M, Blasco M, Serrano M . Cellular senescence in cancer and aging. Cell. 2007; 130(2):223-33. DOI: 10.1016/j.cell.2007.07.003. View

18.

Schmidt J, Cech T . Human telomerase: biogenesis, trafficking, recruitment, and activation. Genes Dev. 2015; 29(11):1095-105. PMC: 4470279. DOI: 10.1101/gad.263863.115. View

19.

Iemitsu M, Maeda S, Jesmin S, Otsuki T, Kasuya Y, Miyauchi T . Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise. J Appl Physiol (1985). 2006; 101(1):151-63. DOI: 10.1152/japplphysiol.00392.2005. View

20.

Bar C, de Jesus B, Serrano R, Tejera A, Ayuso E, Jimenez V . Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction. Nat Commun. 2014; 5:5863. PMC: 4871230. DOI: 10.1038/ncomms6863. View