Does Spin1 mediate L-leucine-effects to ameliorate impaired autophagy?

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: YANAGISAWA Hiroko 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (60416659)
• Co-Investigator(Renkei-kenkyūsha): WATABE Kazuhiko 公益財団法人 東京都医学総合研究所, 運動・感覚システム研究分野・神経変性病理研究室, 室長 (30240477) ; KOMATSU Masaaki 新潟大学, 大学院医歯学総合研究科, 教授 (90356254) ; YAMAMOTO Daisuke 東北大学, 大学院生命科学研究科, 教授 (50318812)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: オートファジー / ロイシン / p62 / Spin1/SPNS / LC3 / ライソゾーム病 / ニーマンピック病C型 / シュワン細胞株

Outline of Final Research Achievements

We have examined the events of autophagy by starvation, adding L-leucine and Spin1 expressing cells in a Schwann cell line (573C10), derived from a model mouse of Niemann-Pick disease type C. We detected an increase of LC3-II and accumulation of p62 in 573C10　cells, in which enlarged lysosome was increased upon serum starvation. Electron microscopic observations revealed that 573C10 cells contain enlarged lysosomes with large vacuoles, which are accompanied by lamellar inclusions composed of aggregated membrane vesicles. We observed that addition of L-leucine or expressing Spin1 ameliorated the enlargement of lysosomes and the p62 accumulation. Then we found the common mechanism for amelioration of defective autophagy, between L-leucine and Spin1.

Free Research Field

医歯薬学分野　　分科　基礎医学　 細目　代謝異常