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chemicals also act as important molecules in signal transduction and gene regula-
tion. Therefore, oxidative stress involves not only direct damages to cellular compo-
nents (proteins, lipids, DNA and others) but also altered signaling pathways and
control mechanisms [ 3 , 105 , 106 ].
As one of the hallmarks of IRI is the huge ROS production, especially at reperfu-sion, exercise-induced adaptations of the myocardial antioxidant buffering system
have been widely investigated. Superoxide dismutases (SOD) are molecules that
promote dismutation of the superoxide radical (.O 2 −) forming hydrogen peroxide
(H 2 O 2 ) and oxygen. Although not a free radical, H 2 O 2 is also a potentially cytotoxic
oxygen-derived molecule, that can be reduced by the enzyme glutathione peroxi-
dase (GPx) or converted into oxygen and water by catalase [ 107 ]. Strong evidence
associate increased activity of the mitochondrial form of SOD (manganese SOD -
MnSOD) to exercise-induced cardioprotection [ 12 , 27 , 99 ]. Importantly, French
et al. [ 27 ] showed that the exercise-induced increase in MnSOD activity attenuated
IR-induced oxidative modification of Ca2+-handling proteins and resulted in
decreased calpain activation and ultimately cardiomyocyte death. The link between
increased MnSOD activity and attenuated calpain activation was confirmed using
MnSOD antisense oligonucleotide treatment. With the knockdown of MnSOD,
protection against calpain activation was abolished and the cardioprotective effect
lost [ 27 ].
Exercise-induced modulation of other antioxidants (such as catalase and gluta-thione peroxidase) and synergistic action of these with different adaptations (stimu-
lation of heat shock proteins, for instance) can also be involved in the cardioprotective
response [ 107 , 108 ]. In addition, exercise variables as intensity and time of detrain-
ing should be considered when evaluating antioxidants involvement in cardiopro-
tection, since each bout of exercise benefits the myocardium for a limited period of
time [ 12 , 20 , 86 ].
5.3 Sarcolemmal and/or Mitochondrial ATP-Sensitive
Potassium Channels
Activity of KAT P channels, highly expressed in the sarcolemma and mitochondria, is
governed by intracellular nucleotides (ATP and ADP) concentration. KAT P channels
remain closed with stable ATP levels; however, metabolic stress-induced (e.g.
hypoxia or ischemia) ATP reduction triggers the channel opening. Cardiomyocytes
K+ efflux hyperpolarizes the cardiac cells and decreases the number of action
potentials. This would limit Ca2+ entrance through L-type channels and prevent
intracellular Ca2+ overload and the MPTP from opening [ 26 , 109 ]. As a result,
cardiac metabolic demand and electron transport chain activity decrease, thereby
preventing ROS production and necrotic cell death. Therefore, KAT P channels are
thought to function as sensors monitoring cellular ionic and bioenergetic balance in
order to preserve cardiac homeostasis during metabolic stress situations [ 23 , 54 ].
J.P. Borges and K. da Silva Verdoorn