title: Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts.
abstract: Taurine is a beta-amino acid found in very high concentration in the heart. Depletion of these intracellular stores results in the development of cardiomyopathy, thought to be mediated by abnormal sarcoplasmic reticular (SR) Ca(2+) transport. There is also evidence that taurine directly alters the Ca(2+) sensitivity of myofibrillar proteins. Major regulators of SR Ca(2+) ATPase (SERCA2a) are the phosphorylation status of a regulatory protein, phospholamban, and SERCA2a expression, which are diminished in the failing heart. The failing heart also exhibits reductions in myofibrillar Ca(2+) sensitivity, a property regulated by the phosphorylation of the muscle protein, troponin I. Therefore, we tested the hypothesis that taurine deficiency leads to alterations in SR Ca(2+) ATPase activity related to reduced phospholamban phosphorylation and expression of SERCA2a. We found that a sequence of events, which included elevated protein phosphatase 1 activity, reduced autophosphorylation of CaMKII, and reduced phospholamban phosphorylation, supports the reduction in SR Ca(2+) ATPase activity. However, the reduction in SR Ca(2+) ATPase activity was not caused by reduced SERCA2a expression. Taurine transporter knockout (TauTKO) hearts also exhibited a rightward shift in the Ca(2+) dependence of the myofibrillar Ca(2+) ATPase, a property that is associated with an elevation in phosphorylated troponin I. The findings support the observation that taurine deficient hearts develop systolic and diastolic defects related to reduced SR Ca(2+) ATPase activity, a change mediated in part by reduced phospholamban phosphorylation.
authors.affiliation: University of South Alabama, College of Medicine, Department of Pharmacology, Mobile, Alabama; and.
authors.forename: K C
authors.initials: KC
authors.lastname: Ramila
authors.affiliation: University of South Alabama, College of Medicine, Department of Pharmacology, Mobile, Alabama; and.
authors.forename: Chian Ju
authors.initials: CJ
authors.lastname: Jong
authors.affiliation: University of South Alabama, College of Medicine, Department of Pharmacology, Mobile, Alabama; and.
authors.forename: Viktor
authors.initials: V
authors.lastname: Pastukh
authors.affiliation: Hyogo University of Health Sciences, School of Pharmacy, Department of Pharmacy, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Hyogo University of Health Sciences, School of Pharmacy, Department of Pharmacy, Kobe, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.affiliation: University of South Alabama, College of Medicine, Department of Pharmacology, Mobile, Alabama; and sschaffe@southalabama.edu.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D056966:Excitation Contraction Coupling; D006321:Heart / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D013654:Taurine / Q000172:deficiency*; D019210:Troponin I / Q000378:metabolism; D000099211:Phospholamban; D000099247:Taurine Transporters
chemical_list: D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013654:Taurine; D019210:Troponin I; D000099211:Phospholamban; D000099247:Taurine Transporters
keywords: cardiomyopathy; phospholamban; protein phosphorylation; sarcoplasmic reticular Ca2+ ATPase activity; taurine; troponin I