TY - JOUR
T1 - Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology
AU - Nicolaou, Persoulla
AU - Hajjar, Roger J.
AU - Kranias, Evangelia G.
PY - 2009/9
Y1 - 2009/9
N2 - The type 1 protein phosphatase (PP1) is a critical negative regulator of Ca2+ cycling and contractility in the cardiomyocyte. In particular, it mediates restoration of cardiac function to basal levels, after β-adrenergic stimulation, by dephosphorylating key phospho-proteins. PP1 is a holoenzyme comprised of its catalytic and auxiliary subunits. These regulatory proteins dictate PP1's subcellular localization, substrate specificity and activity. Amongst them, inhibitor-1 is of particular importance since it has been implicated as an integrator of multiple neurohormonal pathways, which finely regulate PP1 activity, at the level of the sarcoplasmic reticulum (SR). In fact, perturbations in the regulation of PP1 by inhibitor-1 have been implicated in the pathogenesis of heart failure, suggesting that inhibitor-1-based therapeutic interventions may ameliorate cardiac dysfunction and remodeling in the failing heart. This review will discuss the current views on the role of inhibitor-1 in cardiac physiology, its possible contribution to cardiac disease and its potential as a novel therapeutic strategy.
AB - The type 1 protein phosphatase (PP1) is a critical negative regulator of Ca2+ cycling and contractility in the cardiomyocyte. In particular, it mediates restoration of cardiac function to basal levels, after β-adrenergic stimulation, by dephosphorylating key phospho-proteins. PP1 is a holoenzyme comprised of its catalytic and auxiliary subunits. These regulatory proteins dictate PP1's subcellular localization, substrate specificity and activity. Amongst them, inhibitor-1 is of particular importance since it has been implicated as an integrator of multiple neurohormonal pathways, which finely regulate PP1 activity, at the level of the sarcoplasmic reticulum (SR). In fact, perturbations in the regulation of PP1 by inhibitor-1 have been implicated in the pathogenesis of heart failure, suggesting that inhibitor-1-based therapeutic interventions may ameliorate cardiac dysfunction and remodeling in the failing heart. This review will discuss the current views on the role of inhibitor-1 in cardiac physiology, its possible contribution to cardiac disease and its potential as a novel therapeutic strategy.
KW - Ca cycling
KW - Heart failure
KW - Inhibitor-1
KW - Phospholamban
KW - Protein phosphatase-1
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=67650710788&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2009.05.010
DO - 10.1016/j.yjmcc.2009.05.010
M3 - Review article
C2 - 19481088
AN - SCOPUS:67650710788
SN - 0022-2828
VL - 47
SP - 365
EP - 371
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 3
ER -