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Int J Cardiol ; 154(2): 116-21, 2012 Jan 26.
Article in English | MEDLINE | ID: mdl-20875921

ABSTRACT

BACKGROUND: Protein phosphatase 5 (PP5) a serine/threonine phosphatase is ubiquitously expressed in mammalian tissues including the heart, but its physiological role in the heart is still unknown. Therefore, we used a transgenic mouse model to get a first insight into the cardiac role of PP5. METHODS AND RESULTS: We generated transgenic mice with cardiac myocyte specific overexpression of PP5. Successful overexpression of PP5 was demonstrated by Western blotting, immunohistochemistry and enhanced arachidonic acid-stimulated protein phosphatase activity in transgenic hearts. Cardiac function was examined on the level of isolated cardiac myocytes, isolated organs and in intact animals. Whereas Ca(2+) transients and cell shortening remained unchanged, L-type Ca(2+) currents were decreased in isolated cardiac myocytes from transgenic mice. Ventricular contractility was reduced in isolated perfused hearts under basal conditions and after ß-adrenergic stimulation. In intact animals, echocardiography revealed increased left ventricular diameters and decreased contractility and invasively measured hemodynamic performance by left ventricular catheterization demonstrated a reduced response to ß-adrenergic stimulation in transgenic mice compared to wild type. CONCLUSIONS: Overexpression of PP5 affected contractility and ß-adrenergic signaling in the hearts of transgenic mice. Taken together, these findings are indicative of a regulatory role of PP5 in cardiac function.


Subject(s)
Myocardial Contraction/physiology , Myocytes, Cardiac/enzymology , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Phosphoprotein Phosphatases/genetics , Phosphoprotein Phosphatases/metabolism , Animals , Calcium Channels, L-Type/physiology , Gene Expression Regulation, Enzymologic/physiology , Humans , Mice , Mice, Transgenic , Myocytes, Cardiac/cytology , Patch-Clamp Techniques , Rats , Receptors, Adrenergic, beta/metabolism , Signal Transduction/physiology , Transgenes/genetics
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