Phosphorylation of phosphatase type 1 (PP1) regulatory subunit during β-adrenergic stimulation and in the progression to heart failure

LUCOTTI I; SAID M; VITTONE L; RINALDI G; MATTIAZZI A; MUNDIÑA - WEILENMANN C

Buenos Aires

Congreso; XVII Meeting ISHR Latin American Section. XXVII Congreso Nacional de Cardiología; 2009

ISHR Latin American Section - Federacion Argentina de Cardiologia

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 â-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 microg/g) and rats were subjected to aortic constriction (TAC) for 5 months. Propranolol treated mice (40 microg/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