Voluntary exercise may activate components of pro-survival risk pathway in the rat heart and potentially modify cell proliferation in the myocardium.

摘要

Although physical exercise is known to reduce size of infarction,incidence of ventricular arrhythmias, and to improve heartfunction, molecular mechanisms of this protection are not fullyelucidated. We explored the hypothesis that voluntary running,similar to adaptive interventions, such as ischemic or remotepreconditioning, may activate components of pro-survival (RISK)pathway and potentially modify cell proliferation. Sprague-Dawleyadult male rats freely exercised for 23 days in cages equippedwith running wheels, while sedentary controls were housed instandard cages. After 23 days, left ventricular (LV) myocardialtissue samples were collected for the detection of expression andactivation of RISK proteins (WB). The day before, a marker ofcell proliferation 5-bromo-2'-deoxyuridine (BrdU) was given to allanimals 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 BrdUincorporation into DNA was unchanged. In contrast, exercisepromoted pro-apoptotic signaling - enhanced Bax/Bcl-2 ratio andactivation of GSK-3β kinase. Results suggest that in the ratmyocardium adapted to physical load, natural cardioprotectiveprocesses associated with physiological hypertrophy arestimulated, while cell proliferation is not modified. Up-regulationof pro-apoptotic markers indicates potential induction of celldeath mechanisms that might lead to maladaptation in the longterm.