Protection of cardiomyocytes from ischemic/hypoxic cell death via Drbp1 and pMe2 GlyDH in cardio-specific ARC transgenic mice

Jong Ok Pyo, Jihoon Nah, Hyo Jin Kim, Jae Woong Chang, Young Wha Song, Dong Kwon Yang, Dong Gyu Jo, Hyung Ryong Kim, Han Jung Chae, Soo Wan Chae, Seung Yong Hwang, Seung Jun Kim, Hyo Joon Kim, Chunghee Cho, Chang Gyu Oh, Jin Park Woo, Yong Keun Jung

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 α-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 (pMe2GlyDH) 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.

Original languageEnglish (US)
Pages (from-to)30707-30714
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number45
DOIs
StatePublished - Nov 7 2008

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