Although physical exercise is known to reduce size of infarction,
incidence of ventricular arrhythmias, and to improve heart
function, molecular mechanisms of this protection are not fully
elucidated. We explored the hypothesis that voluntary running,
similar to adaptive interventions, such as ischemic or remote
preconditioning, may activate components of pro-survival (RISK)
pathway and potentially modify cell proliferation. Sprague-Dawley
adult male rats freely exercised for 23 days in cages equipped
with running wheels, while sedentary controls were housed in
standard cages. After 23 days, left ventricular (LV) myocardial
tissue samples were collected for the detection of expression and
activation of RISK proteins (WB). The day before, a marker of
cell proliferation 5-bromo-2'-deoxyuridine (BrdU) was given to all
animals to detect its incorporation into DNA of the LV cells
(ELISA). Running increased phosphorylation (activation) of Akt,
as well as the levels of PKCε and phospho-ERK1/2, whereas BrdU
incorporation into DNA was unchanged. In contrast, exercise
promoted pro-apoptotic signaling - enhanced Bax/Bcl-2 ratio and
activation of GSK-3β kinase. Results suggest that in the rat
myocardium adapted to physical load, natural cardioprotective
processes associated with physiological hypertrophy are
stimulated, while cell proliferation is not modified. Up-regulation
of pro-apoptotic markers indicates potential induction of cell
death mechanisms that might lead to maladaptation in the longterm.