2013 Fiscal Year Final Research Report

The roles of class III PI3K in cardiomyocytes

Research Project

Project/Area Number	24790734
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Circulatory organs internal medicine
Research Institution	Akita University
Principal Investigator	KIMURA Hirotaka 秋田大学, 医学(系)研究科(研究院), 非常勤講師 (30382899)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	PIK3C3 / 心肥大 / 心不全 / 心筋症 / ユビキチン化
Research Abstract	We generated cardiomyocyte-specific Pik3c3 knockout (Pik3c3 KO) mice. Pik3c3 KO mice spontaneously developed severe cardiac hypertrophy, dysfunction of contractility, ventricular arrhythmias and sudden death. In Pik3c3 KO hearts, levels of phosphatidylinositol 3-phosphate (PI3P) were reduced. Electronmicroscopic analysis demonstrated that autophagosome was accumulated. Isolated cardiomyocytes were hypertrophic and protein aggregates were deposited in myocardium in the absence of Pik3c3 while proteasome function was normal. This aggregate included proteins degraded via vesicular trafficking, suggesting that Pik3c3 might regulate transport of polyubiquitinated proteins in vesicular trafficking. Similar protein deposition was detected in human cardiac specimen from cases with a heart disease. These findings implied that PIK3C3 deficiency might cause cardiac hypertrophy and heart failure in human.