Molecular cell pharmacology on calcium signaling in diseases

钙离子作为第二信使，通过与大量钙结合蛋白相互作用，至少部分地控制许多生物学过程。这些钙结合蛋白家族由于在各种疾病中表达的不同而引起人们的极大兴趣，但关于钙结合蛋白与疾病的关系尚未见报道，我们首先纯化了S100 C。我们已经克隆了S100 C的cDNA，并确定了S100 C的一级结构，因此我们研究了S100 C在疾病中的生理、药理和病理作用，发现S100 C与普萘洛尔结合，并且普萘洛尔与S100 C结合的浓度相似，其中普萘洛尔具有心脏保护作用。提示S100 C可能是普萘洛尔的胞内靶分子，并具有β受体阻滞作用以外的其他作用。同时发现心肌梗死模型大鼠和缺氧模型大鼠心脏S100 C基因表达发生改变。此外，我们还发现了猪S100 C基因的独特结构。该基因抑制缺氧诱导因子（HIF-1）。提示S100 C可能在心脏病和病理性血管重构中起重要作用。C. W. Heizmann等发现S100 C在疾病细胞和正常细胞中存在差异表达，并发现S100 C的基因表达存在细胞周期依赖性差异，因此S100 C可能在多种疾病中发挥重要作用。

Calcium ions as second messengers contorol many biological processes, at least in part, via intreraction with a large number of calcium-binding proteins. These calcium-binding protein families become of majoc interest because of their different expression in each disease.But it has not been reported about relation disease to calcium-binding protein, 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.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. It sugested that S100C might be intracellular target molecule of propranolol and share other actions than beta-blockade action. We also found that the gene expression of S100C was changed in the heart of myocardial infarction model rats and hypoxia-induced model rats. Moreover, we found a unique structure of the porcine S100C gene. This gene conteins hypoxia-inducible factor (HIF-1). Theses results sugest that S100C might have an impotant role in heart disease.and in pathological vascular remodeling. C.W.Heizmann found differential expression of S100C in disease cells and normal cells and we found cell-cycle dependent differential gene expression of S100C.Thus, S100C might be thought to play an important role in many diseases.