Importance of pyruvate dehydrogenase in the mouse lungs exposed to hyperoxia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15729
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Saitama Medical University
• Principal Investigator: Kobayashi Shingo 埼玉医科大学, 医学部, 助教 (00464727)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 新生児慢性肺疾患 / 高濃度酸素 / ピルビン酸脱水素酵素 / メタボローム

Outline of Final Research Achievements

This study investigated differences in the response to hyperoxic exposure between neonatal and adult mouse lungs using metabolomics analysis. Neonatal and adult mice were exposed to 21% or 95% O2 for four days. Lung tissue samples were collected and analyzed by metabolomics. Pyruvate dehydrogenase (PDH) enzyme activity, PDH kinase (Pdk) 4 mRNA expression levels, Pdk4 protein expression and localization were determined. Levels of pyruvic acid-related metabolites were elevated in the lungs of hyperoxia-exposed adult mice. PDH activity was reduced and Pdk4 mRNA expression levels after hyperoxic exposure were elevated in adult mice. Pdk4 protein levels were increased in adult mouse lungs exposed to hyperoxia and were localized mainly to the epithelium of terminal bronchiole.
Conclusions: Specific metabolites associated with glycolysis and gluconeogenesis were altered after hyperoxia exposure in the lungs of adult mice, but not in neonates.

Free Research Field

新生児学、呼吸器学

Academic Significance and Societal Importance of the Research Achievements

新生仔マウスと成獣マウスの高濃度酸素暴露に対する耐性の違いについて、ピルビン酸代謝経路の違いで一部説明できることが示唆された。この結果から、将来的に、ピルビン酸代謝経路をターゲットとした新生児慢性肺疾患および成人呼吸窮迫症候群の治療法の開発が期待される。