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Protection of Cardiomyocytes from Ischemic/Hypoxic Cell Death via Drbp1 and pMe(2)GlyDH in Cardio-specific ARC Transgenic Mice

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Abstract
The ischemic death of cardiomyocytes is associated in heart disease and heart failure. However, the molecular mechanism underlying ischemic cell death is not well defined. To examine the function of apoptosis repressor with a caspase recruitment domain (ARC) in the ischemic/hypoxic damage of cardiomyocytes, we generated cardio-specific ARC transgenic mice using a mouse alpha-myosin heavy chain promoter. Compared with the control, the hearts of ARC transgenic mice showed a 3-fold overexpression of ARC. Langendoff preparation showed that the hearts isolated from ARC transgenic mice exhibited improved recovery of contractile performance during reperfusion. The cardiomyocytes cultured from neonatal ARC transgenic mice were significantly resistant to hypoxic cell death. Furthermore, the ARC C-terminal calcium-binding domain was as potent to protect cardiomyocytes from hypoxic cell death as ARC. Genome-wide RNA expression profiling uncovered a list of genes whose expression was changed (>2-fold) in ARC transgenic mice. Among them, expressional regulation of developmentally regulated RNA-binding protein 1 (Drbp1) or the dimethylglycine dehydrogenase precursor (pMe(2)GlyDH) affected hypoxic death of cardiomyocytes. These results suggest that ARC may protect cardiomyocytes from hypoxic cell death by regulating its downstream, Drbp1 and pMe2GlyDH, shedding new insights into the protection of heart from hypoxic damages.
Author(s)
Pyo, Jong-OkNah, JihoonKim, Hyo-JinChang, Jae-WoongSong, Young-WhaYang, Dong-KwonJo, Dong-GyuKim, Hyung-RyongChae, Han-JungChae, Soo-WanHwang, Seung-YongKim, Seung-JunKim, Hyo-JoonCho, ChungheeOh, Chang-GyuPark, Woo JinJung, Yong-Keun
Issued Date
2008-11
Type
Article
DOI
10.1074/jbc.M804209200
URI
https://scholar.gist.ac.kr/handle/local/17239
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Citation
Journal of Biological Chemistry, v.283, no.45, pp.30707 - 30714
ISSN
0021-9258
Appears in Collections:
Department of Life Sciences > 1. Journal Articles
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