Pharmacoproteomic mechanisms in stress protein expression induction

在本研究中，我们发现在多种疾病中诱导和引导的应激蛋白系统成为新的药物靶点，并阐明了其分子机制。重点介绍了我们首次克隆的低氧诱导新基因钙结合蛋白S100C和我们新发现的应激蛋白表达诱导，阐明了各种疾病模型血管重塑的药物蛋白质组学机制。并通过对原始药物蛋白质组数据库的整合和药物蛋白质组实验分析，阐明了药物蛋白质组学药物作用的蛋白质组学机制。在低氧处理的肺动脉高压模型中，我们发现通过HIF-1诱导应激蛋白S100C的表达在肺动脉重塑中起重要作用。(《药典》J.3：183-188,2003)。此外，通过代谢组学分析，口服剂量的牛磺酸通过HIF-1抑制S100C的表达和肺动脉重塑，并报告了作为新的肺动脉高压治疗药物的可能性(The Pharmacgenology J.3：183-188,2003)。(发行量。110：1839-1846,2004)。此外，在蛛网膜下腔出血模型中，延迟性脑基底动脉痉挛时应激蛋白HSP72的表达，以及口服抗胃溃疡药物替普瑞酮(Geranylgeranylacetone)更多地诱导了脑基底动脉应激蛋白HSP72的表达，并发现I促进脑血管痉挛(循环)的改善。110：1839-1846,2004)。通过这些研究结果，我们阐明了血管重塑的新的药物蛋白质组学机制。通过本研究提出的药物蛋白质组学数据库和蛋白质组分析，阐明了应激蛋白在各种疾病模型中诱导的药物蛋白质组学机制，并将在不久的将来应用于更广泛的医学研究。

In this study, we have discovered that the stress protein system which induces in various diseases, and is guided becomes novel drug target and have elucidated the molecule mechanism. We exposed a focus to calcium-binding protein S100C which was the new hypoxia-induced gene which we have cloned originally and the other stress protein expression induction that we found newly and elucidated the pharmacoproteomic mechanism of vascular remodeling in various disease model. And I clarified proteome mechanism of pharmacoproteomic drug action by integration of the original pharmacoproteomic database and pharmacoproteomic experimental analysis. In pulmonary hypertension model by hypoxia treatment, we discovered that an expression induction of stress protein S100C through HIF-1 played an important role in remodeling of a pulmonary artery. (The PharmacogenomicsJ.3:183-188,2003). Furthermore, by metabolome analysis, the oral dosage of taurine suppressed the expression of S100C through HIF-1 and remodeling of a pulmonary artery and reported possibility as novel pulmonary hypertension therapeutics (The Pharmacogenomics J.3:183-188,2003). (Circulation. 110:1839-1846,2004). In addition, in a subarachnoid hemorrhage model, expression of stress protein HSP72 in cerebral basilar artery at the time of delayed cerebral basospasm, and the oral dosage of anti gastric ulcer medicine teprenone (Geranylgeranylacetone) induced an expression of stress protein HSP72 in a cerebral basilar artery more and discovered that I promoted improvement of cerebrovasospasm (Circulation. 110:1839-1846,2004). By these results of research, we elucidated novel pharmacoproteomic mechanisms of blood vessel remodeling. We have elucidation pharmacoproteomic mechanisms of stress protein induction in various disease model by pharmacoproteomic database and proteome analysis that we proposed ahead of the world in this study and this research strategy will be applied in more wide medical study in the near future.