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Gadd45beta is a novel mediator of cardiomyocyte apoptosis induced by ischaemia/hypoxia.

Authors
Kim, MY; Seo, EJ; Lee, DH; Kim, EJ; Kim, HS; Cho, HY; Chung, EY; Lee, SH; Baik, EJ; Moon, CH; Jung, YS
Citation
Cardiovascular research, 87(1):119-126, 2010
Journal Title
Cardiovascular research
ISSN
0008-63631755-3245
Abstract
Because apoptotic death plays a critical role in cardiomyocyte loss during ischaemic heart injury, a detailed understanding of the mechanisms involved is likely to have a substantial impact on the optimization and development of treatment strategies. The goal of this study was to assess gene profiling during ischaemia/hypoxia and to evaluate the functions of ischaemia/hypoxia-responsive genes in in vivo and in vitro ischaemia/hypoxia-induced cardiomyocyte apoptosis models.



METHODS AND RESULTS: DNA microarray analysis and real-time polymerase chain reaction were performed on hearts obtained from an in vivo rat transient ischaemia model and on neonatal rat cardiomyocytes from an in vitro hypoxia model. Three genes, namely Ddit4, Gadd45beta and Atf3, were found to be up-regulated in vivo and in vitro. Using loss-of-function and gain-of-function techniques, the functions of these ischaemia/hypoxia-responsive genes were evaluated. Ischaemia/hypoxia-induced cardiomyocyte apoptosis was remarkably attenuated by the small interfering RNA-mediated down-regulation of Gadd45beta in vivo and in vitro, whereas ectopic Gadd45beta expression significantly aggravated hypoxia-induced apoptosis in vitro.



CONCLUSION: These results suggest that Gadd45beta is a key player in ischaemia/hypoxia-induced apoptotic cardiomyocyte death, and that strategies based on its inhibition might be of benefit in the treatment of acute ischaemic heart disease.
MeSH terms
Activating Transcription Factor 3/geneticsAnimalsAnimals, NewbornAntigens, Differentiation/genetics*Antigens, Differentiation/metabolismApoptosis*/geneticsCell HypoxiaCell LineDisease Models, AnimalGene Expression Profiling/methodsGene Knockdown TechniquesHemodynamicsMaleMyocardial Ischemia/genetics*Myocardial Ischemia/metabolismMyocardial Ischemia/pathologyMyocardial Ischemia/physiopathologyMyocytes, Cardiac/metabolism*Myocytes, Cardiac/pathologyOligonucleotide Array Sequence AnalysisRNA InterferenceRatsRats, Sprague-DawleyRepressor Proteins/geneticsTime FactorsTransfectionUp-Regulation
DOI
10.1093/cvr/cvq048
PMID
20154065
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 수환백, 은주문, 창현정, 이숙
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