Protection of cardiomyocytes from ischemic/hypoxic cell death via Drbp1 and pMe2GlyDH in cardio-specific ARC transgenic mice.
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 pMe(2)GlyDH, shedding new insights into the protection of heart from hypoxic damages.
Pyo
Jong-Ok
JO
Creative Research Initiative Acceleration Research, Seoul National University, Shillim-Dong, Seoul 151-747, Korea.
Nah
Jihoon
J
Kim
Hyo-Jin
HJ
Chang
Jae-Woong
JW
Song
Young-Wha
YW
Yang
Dong-Kwon
DK
Jo
Dong-Gyu
DG
Kim
Hyung-Ryong
HR
Chae
Han-Jung
HJ
Chae
Soo-Wan
SW
Hwang
Seung-Yong
SY
Kim
Seung-Jun
SJ
Kim
Hyo-Joon
HJ
Cho
Chunghee
C
Oh
Chang-Gyu
CG
Park
Woo Jin
WJ
Jung
Yong-Keun
YK
D000818:Animals; D016923:Cell Death / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D050893:Dimethylglycine Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
D003598:Cytoskeletal Proteins; D004792:Enzyme Precursors; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C092069:activity regulated cytoskeletal-associated protein; D050893:Dimethylglycine Dehydrogenase; C494399:Dmgdh protein, mouse
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