Elucidation of network in damaged liver involved by novel modification form of D-dopachrome tautomerase

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K00568
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Shimane University
• Principal Investigator: Hiyoshi Mineyoshi 島根大学, 学術研究院医学・看護学系, 助教 (30363162)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: D-ドーパクロムトートメラーゼ / 四塩化炭素 / 肝傷害 / プロテオミクス

Outline of Final Research Achievements

The identity of the novel modification compound to D-dopachrome totemerase (DDT) was clarified using mass spectrometry. It was a condensation compound of carbon tetrachloride (CCl4) metabolite and intravital low molecular weight compound. For the first time in animal tissue, we could assess the modification using mass spectrometry clearly. Analysis of all proteins extracted from rat liver showed that this substance modified for DDT and its family protein, selectively.
Chloroform, which is of concern for daily exposure, is a toxic substance produced by chlorination in the water purification process. Since chloroform and CCl4 pass the same metabolic process, same metabolites are produced. Thus, the same metabolite may be supposed to modify for DDT and its family proteins. It is significant that selective modifications to both proteins were found in the toxic effects, thus, analysis of modification level for both proteins may imply the potential exposure of chloroform and the like.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

日常的な曝露が懸念されるクロロホルムは、浄水処理過程の塩素処理により生じる有毒物質である。クロロホルムは四塩化炭素と同じ代謝過程を経て、同じ代謝産物を生じることから、DDTおよびそのファミリータンパク質に対し、同じ代謝産物を修飾すると考えられる。学術的には、両タンパク質への選択的な修飾が、毒性影響の中で見出されたことに意義があり、社会的には、両タンパク質への修飾レベルの解析がクロロホルム等の潜在的な曝露の評価に有用となる可能性がある点に意義がある。