Pharmacoproteomic mechanisms in stress protein expression induction

在本研究中，我们发现了诱导多种疾病并被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。我们重点研究了我们最初克隆的新缺氧诱导基因钙结合蛋白S100C和我们新发现的应激蛋白表达诱导，阐明了多种疾病模型中血管重构的药物蛋白质组学机制。结合原始药物蛋白质组学数据库和药物蛋白质组学实验分析，阐明了药物蛋白质组学药物作用的蛋白质组学机制。在缺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。(pharmacogenomicsj.3:183 - 188, 2003)。此外，通过代谢组学分析，口服牛磺酸通过HIF-1和肺动脉重塑抑制S100C的表达，并有可能作为一种新的肺动脉高压治疗药物（the Pharmacogenomics j .3:183-188,2003）。(循环。110:1839 - 1846,2004)。此外，在蛛网膜下腔出血模型中，迟发性脑血管痉挛时脑基底动脉中应激蛋白HSP72的表达，口服抗胃溃疡药替普诺酮（香叶酮）更能诱导脑基底动脉中应激蛋白HSP72的表达，发现可促进脑血管痉挛的改善（Circulation. 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。通过药物蛋白质组学数据库和蛋白质组学分析，阐明了应激蛋白诱导各种疾病模型的药物蛋白质组学机制，这一研究策略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.