강종순 (성균관대학교 의과대학, 삼성서울병원) | 한빛사논문 > 한빛사

한빛사논문

조회1,450

성균관대학교 의과대학, 삼성서울병원

CV File 275 kb

Nat. Commun., Published 30 November 2018, 9, Article number: 5107 | https://doi.org/10.1038/s41467-018-07606-y Cardiac specific PRMT1 ablation causes heart failure through CaMKII dysregulation

Jung-Hoon Pyun^1,2, Hyun-Ji Kim^2,3, Myong-Ho Jeong^1,2, Byeong-Yun Ahn^1,2, Tuan Anh Vuong^1,2, Dong I. Lee⁴, Seri Choi⁵, Seung-Hoi Koo⁵, Hana Cho^2,3,6 & Jong-Sun Kang^1,2,6,*

1 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. ² Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. ³ Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419,Korea. ⁴ Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ⁵ Division of Life Sciences, Korea University, Seoul 02841, Korea. ⁶ Samsung Biomedical Institute, Samsung medical center, Seoul 06351, Korea

^*Correspondence to Jong-Sun Kang

Abstract

Dysregulation of Ca²⁺/calmodulin-dependent protein kinase (CaMK)II is closely linked with myocardial hypertrophy and heart failure. However, the mechanisms that regulate CaMKII activity are incompletely understood. Here we show that protein arginine methyltransferase 1 (PRMT1) is essential for preventing cardiac CaMKII hyperactivation. Mice null for cardiac PRMT1 exhibit a rapid progression to dilated cardiomyopathy and heart failure within 2 months, accompanied by cardiomyocyte hypertrophy and fibrosis. Consistently, PRMT1 is downregulated in heart failure patients. PRMT1 depletion in isolated cardiomyocytes evokes hypertrophic responses with elevated remodeling gene expression, while PRMT1 overexpression protects against pathological responses to neurohormones. The level of active CaMKII is significantly elevated in PRMT1-deficient hearts or cardiomyocytes. PRMT1 interacts with and methylates CaMKII at arginine residues 9 and 275, leading to its inhibition. Accordingly, pharmacological inhibition of CaMKII restores contractile function in PRMT1-deficient mice. Thus, our data suggest that PRMT1 is a critical regulator of CaMKII to maintain cardiac function.

논문정보

형식Research article
게재일2018년 11월 (BRIC 등록일 2018-12-11)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

댓글 작성 로그인

CV 열람하기

연락처 보기