Lawler JM, Kwak HB, Kim JH, Suk M. Exercise training inducibility of MnSOD protein expression and activity is retained while reducing prooxidant signaling in the heart of senescent rats. Am J Physiol Regul Integr Comp Physiol 296: R1496-R1502, 2009. First published March 18, 2009; doi:10.1152/ajpregu.90314.2008. While the stress response to heat and exercise is limited in the heart with progressive aging, recent data indicate that acute or short-term exercise upregulates the Mn isoform of superoxide dismutase (MnSOD), which may provide protection against ischemia-reperfusion injury and cell death by reducing oxidative stress. Growing evidence indicates that inducible nitric oxide synthase (iNOS) contributes to age-induced increases in oxidative stress and risk of heart failure. We postulated that oxidative stress and iNOS levels would be related to the ability of the aging heart to upregulate MnSOD in response to long-term exercise training. Six-and twenty-seven-mo-old Fischer-344 rats had been assigned to young sedentary (YS), young exercise (YE), old sedentary (OS), or old exercise (OE) groups. ET groups ran on a treadmill for 60 min/day, 5 days/wk for a total of 12 wk. MnSOD protein expression in the left ventricle was increased (+43%) by 12 wk of exercise training in the old age group, with no changes in Cu, ZnSOD. Exercise training also increased MnSOD activity in left ventricles from old and young rats. HSP70 was inducible by exercise training in hearts exclusively from the young age group. iNOS protein expression increased markedly with aging (+548%), while exercise training decreased iNOS levels by -73% in OE compared with OS. In addition, 4-hydroxynonenal protein adducts in the left ventricle increased by 237% with aging, while 12 wk of exercise training resulted in attenuation (-55%). These data indicate that inducibility of MnSOD is preserved with long-term exercise training in the aging rat heart. Moreover, upregulation of MnSOD in the aging heart was directly associated with attenuated levels of oxidative stress, including iNOS.
