ABSTRACT 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.
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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.
 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
 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.
 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.
 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
 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.
 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.
 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.
 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
 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.
 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.
 Brancaccio, P., Lippi, G. and Maffulli, N. (2010) Biochemical markers of muscular damage. Clinical Chemistry and Laboratory Medicine, 48, 757-767.
 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.
 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.
 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.
 Lappalainen, Z. (2011) Sirtuins: A family of proteins with implications for human performance and exercise physiology. Research in Sports Medicine, 19, 53-65.
 Freyssenet, D. (2007) Energy sensing and regulation of gene expression in skeletal muscle. Journal of Applied Physiology, 102, 529-540.
 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
 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.
 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.
 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
 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.
 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.
 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.
 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.