Elucidation of the mechanisms of copper metabolism during the development and evaluation of acquired effects of copper nutritional status on brain tissue

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16346
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Chiba University
• Principal Investigator: Tanaka Yu-ki 千葉大学, 大学院薬学研究院, 助教 (50824041)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 銅代謝 / 新生児 / 化学形態別分析 / メタロチオネイン / 酸化ストレス

Outline of Final Research Achievements

It is known that copper is highly accumulated in the liver of animals during the fetal to neonatal period compared to that of adult animals. In this study, we found that the copper concentration in the liver of rat neonates decreased to about 1/10 from 2 to 5 weeks of age. Speciation analysis by liquid chromatography hyphenated ICP-mass spectrometry revealed that copper bound to metallothionein in the liver decreased, while copper bound to ceruloplasmin in the serum increased. It was suggested that low expression of the copper chaperone Atox1 in the liver during the neonatal period suppressed copper excretion from the liver. As well as the antioxidant protein Atox1, the expression levels of copper-related proteins can be influenced by the hypoxic conditions during the fetal period, and affect the unique copper metabolism in neonates.

Free Research Field

分析化学

Academic Significance and Societal Importance of the Research Achievements

銅は生体必須元素であり、生物の発生、発達に欠かすことはできない。一方、過剰な銅は生体内でフェントン反応を触媒し、活性酸素種の生成に寄与する。新生仔期に肝臓に過剰蓄積している銅はメタロチオネインに結合した毒性の低い形態で貯蔵されているものの、潜在的には銅が多量に存在しているため、正常な解毒代謝機構が破綻した場合や、栄養としての銅負荷が過剰になった場合には個体への影響が懸念される。本研究の成果によって、新生仔（児）期の特異的な銅代謝状態が明らかにされ、発生や発達に有害な影響を及ぼす可能性のある銅の適切な栄養状態を確保することの重要性が示された。