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Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis.
J Am Coll Cardiol. 2008 Aug 05; 52(6):470-82.JACC

Abstract

OBJECTIVES

The purpose of this study was to study the underlying molecular mechanisms of the protective cardiac effects of physical exercise.

BACKGROUND

Telomere-regulating proteins affect cellular senescence, survival, and regeneration.

METHODS

C57/Bl6 wild-type, endothelial nitric oxide synthase (eNOS)-deficient and telomerase reverse transcriptase (TERT)-deficient mice were randomized to voluntary running or no running wheel conditions (n = 8 to 12 per group).

RESULTS

Short-term running (21 days) up-regulated cardiac telomerase activity to >2-fold of sedentary controls, increased protein expression of TERT and telomere repeat binding factor (TRF) 2, and reduced expression of the proapoptotic mediators cell-cycle-checkpoint kinase 2 (Chk2), p53, and p16. Myocardial and leukocyte telomere length did not differ between 3-week- and 6-month-old sedentary or running mice, but telomerase activity, TRF2 and TERT expression were persistently increased after 6 months and the expression of Chk2, p53, and p16 remained down-regulated. The exercise-induced changes were absent in both TERT(-/-) and eNOS(-/-) mice. Running increased cardiac expression of insulin-like growth factor (IGF)-1. Treatment with IGF-1 up-regulated myocardial telomerase activity >14-fold and increased the expression of phosphorylated Akt protein kinase and phosphorylated eNOS. To test the physiologic relevance of these exercise-mediated prosurvival pathways, apoptotic cardiomyopathy was induced by treatment with doxorubicin. Up-regulation of telomere-stabilizing proteins by physical exercise in mice reduced doxorubicin-induced p53 expression and potently prevented cardiomyocyte apoptosis in wild-type, but not in TERT(-/-) mice.

CONCLUSIONS

Long- and short-term voluntary physical exercise up-regulates cardiac telomere-stabilizing proteins and thereby induces antisenescent and protective effects, for example, to prevent doxorubicin-induced cardiomyopathy. These beneficial cardiac effects are mediated by TERT, eNOS, and IGF-1.

Authors+Show Affiliations

Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18672169

Citation

Werner, Christian, et al. "Effects of Physical Exercise On Myocardial Telomere-regulating Proteins, Survival Pathways, and Apoptosis." Journal of the American College of Cardiology, vol. 52, no. 6, 2008, pp. 470-82.
Werner C, Hanhoun M, Widmann T, et al. Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol. 2008;52(6):470-82.
Werner, C., Hanhoun, M., Widmann, T., Kazakov, A., Semenov, A., Pöss, J., Bauersachs, J., Thum, T., Pfreundschuh, M., Müller, P., Haendeler, J., Böhm, M., & Laufs, U. (2008). Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. Journal of the American College of Cardiology, 52(6), 470-82. https://doi.org/10.1016/j.jacc.2008.04.034
Werner C, et al. Effects of Physical Exercise On Myocardial Telomere-regulating Proteins, Survival Pathways, and Apoptosis. J Am Coll Cardiol. 2008 Aug 5;52(6):470-82. PubMed PMID: 18672169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. AU - Werner,Christian, AU - Hanhoun,Milad, AU - Widmann,Thomas, AU - Kazakov,Andrey, AU - Semenov,Alexander, AU - Pöss,Janine, AU - Bauersachs,Johann, AU - Thum,Thomas, AU - Pfreundschuh,Michael, AU - Müller,Patrick, AU - Haendeler,Judith, AU - Böhm,Michael, AU - Laufs,Ulrich, PY - 2008/02/07/received PY - 2008/03/21/revised PY - 2008/04/14/accepted PY - 2008/8/2/pubmed PY - 2008/9/16/medline PY - 2008/8/2/entrez SP - 470 EP - 82 JF - Journal of the American College of Cardiology JO - J Am Coll Cardiol VL - 52 IS - 6 N2 - OBJECTIVES: The purpose of this study was to study the underlying molecular mechanisms of the protective cardiac effects of physical exercise. BACKGROUND: Telomere-regulating proteins affect cellular senescence, survival, and regeneration. METHODS: C57/Bl6 wild-type, endothelial nitric oxide synthase (eNOS)-deficient and telomerase reverse transcriptase (TERT)-deficient mice were randomized to voluntary running or no running wheel conditions (n = 8 to 12 per group). RESULTS: Short-term running (21 days) up-regulated cardiac telomerase activity to >2-fold of sedentary controls, increased protein expression of TERT and telomere repeat binding factor (TRF) 2, and reduced expression of the proapoptotic mediators cell-cycle-checkpoint kinase 2 (Chk2), p53, and p16. Myocardial and leukocyte telomere length did not differ between 3-week- and 6-month-old sedentary or running mice, but telomerase activity, TRF2 and TERT expression were persistently increased after 6 months and the expression of Chk2, p53, and p16 remained down-regulated. The exercise-induced changes were absent in both TERT(-/-) and eNOS(-/-) mice. Running increased cardiac expression of insulin-like growth factor (IGF)-1. Treatment with IGF-1 up-regulated myocardial telomerase activity >14-fold and increased the expression of phosphorylated Akt protein kinase and phosphorylated eNOS. To test the physiologic relevance of these exercise-mediated prosurvival pathways, apoptotic cardiomyopathy was induced by treatment with doxorubicin. Up-regulation of telomere-stabilizing proteins by physical exercise in mice reduced doxorubicin-induced p53 expression and potently prevented cardiomyocyte apoptosis in wild-type, but not in TERT(-/-) mice. CONCLUSIONS: Long- and short-term voluntary physical exercise up-regulates cardiac telomere-stabilizing proteins and thereby induces antisenescent and protective effects, for example, to prevent doxorubicin-induced cardiomyopathy. These beneficial cardiac effects are mediated by TERT, eNOS, and IGF-1. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/18672169/Effects_of_physical_exercise_on_myocardial_telomere_regulating_proteins_survival_pathways_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(08)01786-5 DB - PRIME DP - Unbound Medicine ER -