令和6年度_2024_助成研究報告集
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Abstractはじめに脂質はポストゲノム時代においての重要な研究対象となっている.脂質の量はその合成や分解を担う代謝酵素により制御されているため,脂質の生理機能や疾患との関連を明らかにするためには,脂質代謝酵素の性質についての詳細な理解が必要である.東京理科大学創域理工学部・生命生物科学科中村研究室・助教Tokyo university of Science金丸 佳織Kaori Kanemaru― 215 ―Lipids have emerged as key regulatory molecules in the post-genomic era, and their biological functions are intricately linked to the activity of metabolic enzymes responsible for their synthesis and degradation. Phospholipase C (PLC), a well-characterized lipid-metabolizing enzyme, hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) on the inner leaflet of the plasma membrane, regulating various cellular functions through second messenger signaling. In this study, we investigated a previously uncharacterized bacterial-type PLC-like protein secreted from cells. Unlike conventional PLCs, this protein does not metabolize PIP2 but instead targets other phosphoinositides. We found that its enzymatic activity enhances the production of extracellular vesicles (EVs), which in turn promote its own secretion via a non-classical pathway. Moreover, the protein appears to facilitate the removal of unnecessary or misfolded proteins from the cytoplasm. In knockout mice lacking this gene, increased oxidative stress and markers of cellular senescence were observed in the retina and liver. Given that intracellular accumulation of damaged proteins is a known trigger of senescence and is implicated in various diseases, our findings suggest that this bacterial-type PLC-like protein plays a protective role in protein homeostasis. Further elucidation of its mechanism may contribute to novel therapeutic approaches for age-related and protein-aggregation diseases.分泌性イノシトールリン脂質代謝酵素の生理機能解析Analysis of the Physiological Functions of Secretory Inositol Lipid-Metabolizing Enzymes

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