Molecularphysiological analysis of calcium-signaling proteins in cardiac sarcoplasmic reticulum

我们研究了心肌肌浆网（SR）蛋白调控的分子机制，SR在心肌兴奋-收缩偶联中起关键作用。钙信号在调节心脏特性中的生理作用：我们研究了抗磷酸蛋白单克隆抗体对心脏SR钙泵atp酶活性的影响。磷酸蛋白是心脏SR钙信号蛋白之一。我们发现该抗体抑制了两个SR蛋白之间的直接蛋白相互作用（J. Mol. Cell.）。心脏杂志。23,1223,1991)。我们研究了合成磷蛋白肽对atp酶的影响。揭示了多磷膦碱对钙泵atp酶的双重调控作用；V_<max>为胞质结构域，K_<Ca>为膜内结构域[j]。化学。267,1647,1992)。正常和应激心肌细胞Ca调控系统在心肌SR中的病理作用：建立离体心肌细胞胞内Ca^<2+>含量测定系统，评价心肌细胞在缺氧和Ca超载情况下的细胞内Ca^<2+>瞬时态。目前，我们正在评估抗磷蛋白单克隆抗体和合成肽对Ca^<2+>瞬态的影响。我们正在研究正常、应激或心肌炎心肌细胞中心脏SR - Ca信号蛋白表达的调控。

We investigated the molecular mechanism of regulation of the proteins of cardiac sarcoplasinic reticulum (SR) which has pivotal role in excitation-contraction coupling of myocardium.1. Physiological roles of Ca signaling in regulation of cardiac property : We investigated the effects of a monoclonal antibody against phospholamban, one of the Ca signaling proteins in cardiac SR, on ATPase activity of cardiac SR Ca pump ATPase. We found that the antibody inhibit the direct protein-protein interaction between the two SR proteins (J. Mol. Cell. Cardiol. 23, 1223, 1991). We investigated the effects of synthetic phospholamban peptides on the ATPase. The dual regulatory effects of pliospholainban on Ca pump ATPase were revealed ; the cytoplasmic domain for V_<max> and the intramembrane domain for K_<Ca> (J. Biol. Chem. 267, 1647, 1992).2. Pathological roles of Ca regulatory system of cardiac SR in normal and stressed inyocytes : We established the intracellular Ca^<2+> content measuring system in isolated cardiac myocyte, and evaluated intracellular Ca^<2+> transients of cardiac myocyte under hypoxia and Ca overload. Currently, we are on the way to evaluate the effect of anti-phospholamban monoclonal antibody and the synthetic peptides on the Ca^<2+> transient. We are examining the regulation of the expression of cardiac SR Ca signaling proteins in normal, stressed, or cardioinyopatliic cardiomyocyte.