CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Phosphorylation of phosphatase type 1 (PP1) regulatory subunit during â-adrenergic stimulation and in the progression to heart failure
LUCOTTI I; SAID M; VITTONE L; RINALDI G; MATTIAZZI A; MUNDIÑA - WEILENMANN C
Ciudad Atónoma de Buenos Aires
Congreso; XVII Meeting ISHR Latin American Section to be held with the XXVII National Congress of Cardiology (FAC); 2009
Latin American Section of the ISHR
In the heart, Ca2+ cycling and contractility are controlled by a fine balance of protein kinase and phosphatase (PPs) activities. The mechanism of regulation of the activity of PP1, the main phosphatase in the myocardium, is not clear. PP1 consists of a catalytic subunit (PP1c) complexed to a regulatory subunit (PP1Gm). PP1Gm localizes PP1c to specific subcellular sites near its substrates. Upon phosphorylation of PP1Gm, the interaction PP1c-PP1Gm is altered and PP1 activity is modified. To asses whether changes in PP1Gm phosphorylation occur during b-adrenergic stimulation or in the progression to heart failure, situations in which PPs have been reported to be altered, mice were injected with adrenaline (0.5 ug/g) and rats were subjected to aortic constriction (TAC) for 5 months. Propranolol treated mice (40 ug/g) and SHAM operated rats were used as respective controls. Adrenaline treatment produced a 7.7 fold increase in the phosphorylation of Ser67 of PP1Gm, immunodetected by phosphospecific antibodies with no change in the expression of the protein. Rats with TAC also showed an increase in Ser67 phosphorylation of PP1Gm (130±8.8%, n=5 respect to SHAM rats p<0.05) which ocurred together with an increase in the phosphorylation of Ser16 of phospholamban, the main substrate for PP1 (196.8±31.9%, n=8 vs. SHAM rats, p<0.05) The results indicate that in cardiac muscle, phosphorylation of PP1Gm could be a mechanism regulating PP1 activity, whose main substrate, PLN, is critical in the control of myocardial relaxation and contractility.