Protein phosphatase activity is increased in a rat model of long-term β-adrenergic stimulation.

Autor: Bokník, Peter, Fockenbrock, Markus, Herzig, Stefan, Knapp, Jörg, Linck, Bettina, Lüss, Hartmut, Müller, Frank Ulrich, Möller, Thorsten, Schmitz, Wilhelm, Schröder, Frank, Neumann, Joachim
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Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology; Sep2000, Vol. 362 Issue 3, p222-231, 10p
Abstrakt: We tested the hypothesis that altered phosphorylation of Ca2+ regulatory proteins contributes to contractile anomalies in cardiac hypertrophy. Cardiac hypertrophy was induced in rats by chronic s.c. administration of isoproterenol (Iso, 2.4 mg/kg/day) via osmotic minipumps. On day 2 of Iso treatment the expression of atrial natriuretic factor was increased, time of relaxation in isolated papillary muscles shortened and protein expression of phospholamban (PLB) and sarcoplasmic reticulum Ca2+-ATPase reduced. In addition, the phosphorylation state of PLB at serine-16 and threonine-17 was decreased from (arbitrary units) 2.3±0.3 to 1.1±0.2 and from 4.1±0.6 to 2.1±0.2, respectively. This was not accompanied by altered activity of PLB-phosphorylating protein kinases (protein kinase A or Ca2+/calmodulin-dependent protein kinase II), whereas the activity of types 1 and 2A protein phosphatases (PP1 and -2A respectively) was enhanced from 1.1±0.08 to 1.71±0.13 nmol/mg/min. Iso treatment did not alter the PP1/PP2A activity ratio and 1 nmol/l okadaic acid, a concentration which completely blocks the catalytic subunit of PP2A, inhibited about 40% of total PP activity in all groups studied. These data indicate that the activity of both PP1 and PP2A were increased. All effects of Iso treatment were abolished by co-administration of propranolol (29.7 mg/kg/day). It is concluded that dephosphorylation of PLB is due to enhanced activity of PP1 and PP2A. We suggest that chronic β-adrenergic stimulation, which occurs in human cardiac hypertrophy and failure, can lead to increased activity of PPs. This may contribute to altered contractile responses in the hypertrophied heart. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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