Analysis of carbon monoxide toxicity using water-soluble CORMs

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04147
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Aki Toshihiko 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (60304474)
• Co-Investigator(Kenkyū-buntansha): 鵜沼 香奈 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (30586425) ; 船越 丈司 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40444715) ; 則竹 香菜子 東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (40758067)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 一酸化炭素 / CORM-3 / フィブロネクチン / p62

Outline of Final Research Achievements

Carbon monoxide is a toxic gas, due to its high affinity to heme and resultant inhibition of binding of oxygen to heme. On the other side, carbon monoxide is generated in human body and has protective roles against stresses. Water soluble carbon monoxide releasing molecules (CORMs) has been attracted much attention due to its easy use for experiments. We found that exposure of a high concentration of CORM-3 to cells resulted in the aggregation of p62 as well as fibronectin. Since these two molecules are essential to autophagy as well as formation of extracellular matrix, CORM-3 should impairs these processes when applied to cells at high concentrations.

Free Research Field

法医学・分子細胞毒性学

Academic Significance and Societal Importance of the Research Achievements

一酸化炭素は近年、その毒性よりむしろ低濃度における細胞・臓器保護作用が注目を集め、各種一酸化炭素発生剤が開発されてきた。その中でも水溶性一酸化炭素発生剤であるCORM-A1, CORM-3はその実用性から注目を集めている。本研究で、CORM-3には高濃度で用いた場合にある特定のタンパク質に凝集体形成を誘導する作用があることが判明し、水溶性一酸化炭素発生剤の適正な使用法への一助になったものと考えられる。