Cardiac specific PRMT1 ablation causes heart failure through CaMKII dysregulation

Jung-Hoon Pyun, Hyun-Ji Kim, Myong-Ho Jeong, Byeong-Yun Ahn, Tuan Anh Vuong, Dong I. Lee, Seri Choi, Seung-Hoi Koo, Hana Cho and Jong-Sun Kang ()
Additional contact information
Jung-Hoon Pyun: Sungkyunkwan University School of Medicine
Hyun-Ji Kim: Single Cell Network Research Center, Sungkyunkwan University School of Medicine
Myong-Ho Jeong: Sungkyunkwan University School of Medicine
Byeong-Yun Ahn: Sungkyunkwan University School of Medicine
Tuan Anh Vuong: Sungkyunkwan University School of Medicine
Dong I. Lee: Johns Hopkins University School of Medicine
Seri Choi: Korea University
Seung-Hoi Koo: Korea University
Hana Cho: Single Cell Network Research Center, Sungkyunkwan University School of Medicine
Jong-Sun Kang: Sungkyunkwan University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07606-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07606-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07606-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().