Molecular cell pharmacology on Novel calcium signaling

钙信号部分通过钙结合蛋白家族传递到细胞内的反应中，这些蛋白被认为调节各种生物过程。这些钙结合蛋白家族因其在各种疾病中的不同表达而备受关注。但与我们首次提纯的S100C有关的疾病尚未见报道。我们已经克隆了S100C的cDNA，并确定了S100C的第一个结构，因此我们对S100C在疾病中的生理、药理和病理作用进行了研究。普萘洛尔的心脏保护作用目前被认为不依赖于它的β-受体阻滞剂作用，而是通过与心肌的直接相互作用发挥作用，但其作用途径尚不清楚。我们发现S100C与普萘洛尔结合，普萘洛尔与S100C结合的浓度与文献报道的普萘洛尔具有心脏保护作用的浓度相似。心得安浓度低于需要与钙调素或肌钙蛋白c等钙结合蛋白相互作用的浓度，提示S100C可能是心得安的细胞内靶分子，除参与B-受体阻断作用外，还具有其他作用。我们还发现，与正常大鼠相比，心肌梗死模型大鼠心脏中S100C的基因表达发生了变化。这些结果提示S100C可能在心脏病中起重要作用。我们证明S100L是一种新型的选择性嗜酸性趋化因子，在所有趋化蛋白中对豚鼠嗜酸性粒细胞具有最强的趋化活性。C.W.Heizmann发现S100L在肿瘤细胞和正常细胞中的差异表达，我们发现S100C的差异表达依赖于细胞周期，因此，S100C和S100L可能在许多疾病中发挥重要作用。

The calcium signal is transmitted into the intracellular response in part via families of calcium-binding proteins which are thought to regulate a variety of biological processes. These calcium-binding protein families become of major interest because of their different expression in each disease. But it has not been reported about relation disease to S100C we first purified. we already cloned cDNA for S100C and decided the first structure of S100C.So we studied about physiological, pharmacological and pathological roles of S100C in diseases.The cardioprotective effect of propranolol is now believed to be independent on its BETA-blocking effect and exert through the direct interaction wuth cardiac muscle, but the pathway of its action remains unclear. We found that S100C bound to propranolol and that the concentrations of propranolol for binding with S100C was similar in which propranolol was reported to exert cardioprotective effects. The concentration of propranolol was lower than those to need to interact with other calcium-binding proteins, such as calmodulin or troponin c. It sugested that S100C might be intracellular target molecule of propranolol and share other actions than B-blockade action. we also found that the gene expression of S100C was changed in the heart of myocardial infarction model rats compared with normal rats. Theses results sugest that S100C might have an important role in heart disease. And we demonstrated that S100L was a novel selective eosinophilic chemotactic factor, and had a most potent chemotactic activity on guinea pig eosinophils of all the chemotactic proteins. C.W.Heizmann found differential expression of S100L in tumor cells and normal cells and we found cell-cycle dependent differential gene expression of S100C.Thus, S100C and S100L might be thought to play an important role in many diseases.