The functional regulation of metallothionein by functional organic-inorganic hybrid molecules and its molecular mechanism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Tokyo University of Pharmacy and Life Science (2014); Aichi Gakuin University (2012-2013)
• Principal Investigator: FUJIWARA Yasuyuki 東京薬科大学, 薬学部, 教授 (40247482)
• Co-Investigator(Renkei-kenkyūsha): UCHIYAMA Masanobu 東京大学, 薬学部, 教授 (00271916) ; YASUIKE Shuji 愛知学院大学, 薬学部, 教授 (10230210) ; NAKA Hiroshi 名古屋大学, 物質科学国際研究センター, 助教 (70431517) ; LEE Jin-Yong 愛知学院大学, 薬学部, 講師 (80581280)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 薬学 / 有機金属化合物 / 錯体分子 / メタロチオネイン / 血管内皮細胞 / 生体防御因子 / 動脈硬化

Outline of Final Research Achievements

In the present study, out of 120 compounds, we found that Cu(II)(Edtc)2 (Cu10), a organic-inorganic hybrid molecule, strongly induces metallothionein (MT) synthesis without non specific cell damage in human vascular endothelial cells. We also showed that Cu10 is easily taken up by vascular endothelial cells, and that Cu10 induce MT synthesis via metal response element-binding transcription factor-1 (MTF-1) pathway but not Nrf-2 pathway. Cu10 also induces MT synthesis in other cell types such as human brain microvascular pericytes and human coronary artery smooth muscle cells. However, the stimulatory effect of Cu10 was weaker than Cu10-stimulated vascular endothelial cells, suggesting that Cu10 has more strong activity on MT synthesis in vascular endothelial cells. These observations suggest that Cu10, a organic-inorganic hybrid molecule, may have a potential to contribute for prevention of vascular diseases including atherosclerosis.

Free Research Field

環境毒性学