Studies on the association of lipid hydroperoxides and Alzheimer's disease by LC/MS

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16531
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Hokkaido University
• Principal Investigator: Chen Zhen 北海道大学, 保健科学研究院, 講師 (60802634)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: oxidative stress / oxidized lipids / lipid hydroperoxides / lipidomics / plasmalogen / antioxidant / LC/MS / PC12 neuronal cells

Outline of Final Research Achievements

Alzheimer's disease (AD) is a serious threat worldwide, in which oxidative stress is thought to play an important role in the pathological development. In this study, the AD cell model by using PC12 neuronal cells was established, the intracellular intact lipids and oxidized lipids were detected by LC/MS, and the contents of the molecular species were determined. Besides, cell morphology, viability, and reactive oxygen species levels were evaluated. As a result, lipid hydroperoxide molecular species accumulated with the increased H2O2 concentration, suggesting the oxidative damage in the molecular level. Moreover, the amounts of functional lipids including plasmalogens and cardiolipins were decreased along with the increased H2O2 concentration. This study showed that the lipid metabolism disorders occurred in AD model neurons, which suggested a close association between lipid hydroperoxides and AD.

Free Research Field

Analytical chemistry

Academic Significance and Societal Importance of the Research Achievements

ADは世界中で深刻な社会問題となり、ADのメカニズムに関する研究は人類の健康増進に貢献できる。本研究では、LC/MSによる確立されたリピドミクス分析方法を用いて、ADモデル神経細胞を対象に、病態による神経細胞の変化と酸化ストレスにおける過酸化脂質の量の変動の関連を研究した。酸化ストレスに受けた神経細胞内では未酸化脂質や過酸化脂質の網羅的に定性と定量をすることで、ADに関連する脂質代謝異常として分子レベルの病理メカニズムの解明が期待される。また、脂質の定性・定量評価を用い、ADに罹患する潜在的なリスクの予測や診断、及び薬物治療効果の評価に有用な指標になると考えられる。