The modulation of sirtuins and apoptotic proteins in rats after exhaustive exercise


A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circu- lating human lymphocytes leading to lipid peroxide- tion, DNA damage, mitochondrial perturbations, and protein oxidation. In a training experiment, Wistar rats were divided into control group (CG) and exer- cise group (EG). After a running level exercise until exhaustion, we observed an increase in the mRNA content and protein expression of SIRT1 and SIRT7 in the EG compared to the CG. Moreover, such train- ing exercise did not change mRNA transcripts and protein expression of FOXO3A and GADD45. We also observed an increase of pro-apoptotic protein bax and a decrease of the anti-apoptotic protein bcl-2 in the EG. Accordingly, we observed a caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage only in EG rats. Statistical analysis of the data showed a significant correlation between SIRT1 and SIRT7 expression and apoptotic proteins such as bax, bcl-2 in both tissues. We conclude that, in both muscle, such exercise activates both a damaging apoptotic mecha- nism with bax increase and bcl-2 decrease and a counterbalancing protective mechanism with SIRT1 and SIRT7 increase.

Share and Cite:

Marfe, G. , Manzi, V. , Tafani, M. , Pucci, B. , Gambacurta, A. , Antonio Russo, M. and Sinibaldi-Salimei, P. (2012) The modulation of sirtuins and apoptotic proteins in rats after exhaustive exercise. Open Journal of Molecular and Integrative Physiology, 2, 65-74. doi: 10.4236/ojmip.2012.23010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Gomez-Cabrera, M.C., Vi?a, J. and Ji, L.L. (2009) Interplay of oxidants and antioxidants during exercise: Implications for muscle health. Physician and Sportsmedicine, 37, 116-123. doi:10.3810/psm.2009.12.1749
[2] Huang, C.C., Lin, T.J., Chen, C.C. and Lin, W.T. (2009) Endurance training accelerates exhaustive exercise-induced mitochondrial DNA deletion and apoptosis of left ventricle myocardium in rats. European Journal of Applied Physiology, 107, 697-706. doi:10.1007/s00421-009-1177-4
[3] Neto, R.J.C., Lira, F.S., Oyama, L.M., Zanchi, N.E., Yamashita, A.S., Batista, M.L. Jr., do Nascimento, C.M.O. and Seelaender, M. (2009) Exhaustive exercise causes an anti-inflammatory effect in skeletal muscle and a pro-inflammatory effect in adipose tissue in rats. European Journal of Applied Physiology, 106, 697-704. doi:10.1007/s00421-009-1070-1
[4] Higashihara, A., Ono, T., Kubota, J., Okuwaki, T. and Fukubayashi, T. (2010) Functional differences in the activity of the hamstring muscles with increasing running speed. Journal of Sports Science and Medicine, 28, 10851092. doi:10.1080/02640414.2010.494308
[5] Kimball, S.R. and Jefferson, L.S. (2010) Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise. Journal of Biological Chemistry, 285, 29027-29032.
[6] Reichhold, S., Neubauer, O., Bulmer, A.C., Knasmüller, S. and Wagner, K.H. (2009) Endurance exercise and DNA stability: Is there a link to duration and intensity? Mutation Research, 682, 28-38. doi:10.1016/j.mrrev.2009.02.002
[7] Marfe, G., Tafani, M., Pucci, B., Di Stefano, C., Indelicato, M., Andreoli, A., Russo, M.A., Sinibaldi-Salimei, P. and Manzi, V. (2010) The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational longdistance runners. BMC Physiology, 10, 7. doi:10.1186/1472-6793-10-7
[8] Zou, J., Yuan, J., Lv, S. and Tu, J. (2010) Effects of exercise on behavior and peripheral blood lymphocyte apoptosis in a rat model of chronic fatigue syndrome. Journal of Huazhong University of Science and Technology, 30, 258-264. doi:10.1007/s11596-010-0225-y
[9] Liang, H., Balas, B., Tantiwong, P., Dube, J., Goodpaster B.H., O’Doherty, R.M., DeFronzo, R.A., Richardson, A., Musi, N. and Ward, W.F. (2009) Whole body overexpression of PGC-1alpha has opposite effects on hepatic and muscle insulin sensitivity. American Journal of Physiology—Endocrinology and Metabolism, 96, E945-E954.
[10] Quadrilatero, J., Bombardier, E., Norris, S.M., Talanian, J.L., Palmer, M.S., Logan, H.M., Tupling, A.R., Heigenhauser, G.J. and Spriet, L.L. (2010) Prolonged moderateintensity aerobic exercise does not alter apoptotic signaling and DNA fragmentation in human skeletal muscle. American Journal of Physiology—Endocrinology and Metabolism, 298, E534-E547.
[11] Brancaccio, P., Lippi, G. and Maffulli, N. (2010) Biochemical markers of muscular damage. Clinical Chemistry and Laboratory Medicine, 48, 757-767. doi:10.1515/cclm.2010.179
[12] Little, J.P., Safdar, A., Cermak, N., Tarnopolsky, M.A. and Gibala, M.J. (2010) Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, 298, R912-R917.
[13] J?rgensen, S.B., Wojtaszewski, J.F., Viollet, B., Andreelli, F., Birk, J.B., Hellsten, Y., Schjerling, P., Vaulont, S., Neufer, P.D., Richter, E.A. and Pilegaard, H. (2005) Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle. FASEB Journal, 19, 1146-1148.
[14] Tran, H., Brunet, A., Grenier, J.M., Datta, S.R., Fornace, A.J. Jr., DiStefano, P.S., Chiang, L.W. and Greenberg, M.E. (2002) DNA repair pathway stimulated by the forkhead transcription factor FOXO3A through the GADD45 protein. Science, 296, 530-534. doi:10.1126/science.1068712
[15] Lappalainen, Z. (2011) Sirtuins: A family of proteins with implications for human performance and exercise physiology. Research in Sports Medicine, 19, 53-65. doi:10.1080/15438627.2011.536068
[16] Freyssenet, D. (2007) Energy sensing and regulation of gene expression in skeletal muscle. Journal of Applied Physiology, 102, 529-540. doi:10.1152/japplphysiol.01126.2005
[17] Brunet, A., Sweeney, L.B., Sturgill, J.F., Chua, K.F., Greer, P.L., Lin, Y., Tran, H., Ross, S.E., Mostoslavsky, R., Cohen, H.Y., Hu, L.S., Cheng, H.L., Jedrychowski, M.P., Gygi, S.P., Sinclair, D.A., Alt, F.W. and Greenberg, M.E. (2004). Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 303, 2011-2015. doi:10.1126/science.1094637
[18] Lee, J.H., Song, M.Y., Song, E.K., Kim, E.K., Moon, W.S., Han, M.K., Park, J.W., Kwon, K.B. and Park, B.H. (2009) Overexpression of SIRT1 protects pancreatic betacells against cytokine toxicity by suppressing the nuclear factor-kappaB signaling pathway. Diabetes, 58, 344-351. doi:10.2337/db07-1795
[19] Radak, Z., Chung, H.Y. and Goto, S. (2008) Systemic adaptation to oxidative challenge induced by regular exercise. Free Radical Biology and Medicine, 44, 153-159. doi:10.1016/j.freeradbiomed.2007.01.029
[20] Suwa, M., Nakano, H., Radak, Z. and Kumagai, S. (2008) Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism, 57, 986-998. doi:10.1016/j.metabol.2008.02.017
[21] Vakhrusheva, O., Smolka, C., Gajawada, P., Kostin, S., Boettger, T., Kubin, T., Braun, T. and Bober, E. (2008) Inflammatory cardiomyopathy in mice SIRT7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circulation Research, 102, 703-710.
[22] Pillai, J.B., Gupta, M., Rajamohan, S.B., Lang, R., Raman, J. and Gupta, M.P. (2006) Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy. American Journal of Physiology—Heart and Circulatory Physiology, 291, H1545H1553.
[23] Wang, F., Nguyen, M., Qin, F.X. and Tong, Q. (2007) SIRT2 deacetylates FOXO3A in response to oxidative stress and caloric restriction. Aging Cell, 6, 505-514. doi:10.1111/j.1474-9726.2007.00304.x
[24] Dumke, C.L., Mark, D.J., Angela, M.E., Nieman, D.C., Carmichael, M.D., Quindry, J.C., Travis, T.N., Utter, A..C, Gross, G.S.J., Henson, D.A., McAnulty, S.R. and McAnulty, L.S. (2009) Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis. European Journal of Applied Physiology, 107, 419-427. doi:10.1007/s00421-009-1143-1

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.