Alterations in Protein Phosphorylation in the Taurine Deficient Heart.

摘要

We have recently revealed that hearts containing negligible total tissue taurine content demonstrate the characteristics of failing hearts and develop cardiomyopathy over time, but the mechanisms are not well defined. We propose that taurine depletion alters the phosphorylation of proteins that are involved in cardiac excitation contraction coupling and impairs contractile function. To test this hypothesis, we used the taurine transporter knockout (TauTKO) mouse model developed by Ito, et al. (2008). Taurine depletion was found to promote troponin I (TnI) phosphorylation which contributes to decreased muscle protein Ca2+ sensitivity. Similarly, taurine depletion led to reduced sarcoplasmic reticular Ca2+ATPase (SERCA) activity by decreasing the phosphorylation of phospholamban (PLB). This leads to impaired SR Ca 2+ handling ultimately leading to contractile dysfunction. Those events are due, in part, to the activation of protein kinase C (PKC) isozymes and protein phosphatase 1 (PP1). A likely mediator of these changes in the phosphorylation state is the effect of taurine depletion on phospholipid content and oxidative stress, which are the direct activators of PKC and PP1.