Analysis of autophagic dysfunction in skeletal muscles from Pompe disease mice by using blood ubiquitin-protein conjugates

Research Project

Project/Area Number	22791005
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Jikei University School of Medicine
Principal Investigator	SHIMADA Yohta 東京慈恵会医科大学, 医学部, 助教 (20560824)
Project Period (FY)	2010 – 2011
Project Status	Completed (Fiscal Year 2011)
Budget Amount *help	¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	遺伝 / 先天異常学 / ポンペ病 / ユビキチン / オートファジー / 先天代謝異常症 / ユビキチン化タンパク質
Research Abstract	In this study, we tried to evaluate the autophagic dysfunction in skeletal muscle from Pompe disease mice by using blood ubiquitin-protein conjugates.(1) We found that the levels of 58 kDa ubiquitin-protein conjugates in plasma from Pompe disease mice were increased prior to pathological accumulation of autophagosomes in skeletal muscles.(2) We found that levels of 58 kDa proteins were increased in skeletal muscles as well as plasma from Pompe disease mice, and these proteins were localized to autophagosomes accumulated in skeletal muscle fibers from Pompe disease mice.(3) These findings suggested that analysis of 58 kDa ubiquitin-protein conjugates in plasma may be able to detect the autophagic dysfunction in skeletal muscles and be more sensitive than immunohistochemical analysis of skeletal muscles.