Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury.
10.3858/emm.2009.41.4.027
- Author:
Mi Jin LEE
1
;
Yong Keun KWAK
;
Kyung Ran YOU
;
Byung Ho LEE
;
Dae Ghon KIM
Author Information
1. Division of Hepatology and Gastroenterology, Department of Internal Medicine, The Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Korea. daeghon@moak.chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
ANKRD1 protein, human;
apoptosis;
heart;
reperfusion injury;
transcription factor CHOP
- MeSH:
Animals;
Animals, Newborn;
Anoxia;
Apoptosis/physiology;
Cells, Cultured;
Humans;
Male;
*Myocardial Reperfusion Injury/metabolism/pathology;
*Myocardium/metabolism/pathology;
Myocytes, Cardiac/cytology/metabolism;
Nuclear Proteins/genetics/*metabolism;
Promoter Regions, Genetic;
Rats;
Rats, Sprague-Dawley;
Repressor Proteins/genetics/*metabolism;
Transcription Factor AP-1/genetics/metabolism;
Transcription Factor CHOP/genetics/*metabolism
- From:Experimental & Molecular Medicine
2009;41(4):243-252
- CountryRepublic of Korea
- Language:English
-
Abstract:
Oxidative stress is critical for causing cardiac injuries during ischemia-reperfusion (IR), yet the molecular mechanism for this remains unclear. In the present study, we observe that hypoxia and reoxygenation, a component of ischemia, effectively induces apoptosis in the cardiac myocytes from neonatal rats and it concomitantly leads to induction of GADD153, an apoptosis-related gene. Furthermore, IR injury of rat heart showed a GADD153 overexpression in the ischemic area where the TUNEL reaction was positive. A downregulation of cardiac ankyrin repeat protein (CARP) was also observed in this ischemic area. Promoter deletion and reporter analysis revealed that hypoxia transcriptionally activates a GADD153 promoter through the AP-1 element in neonatal cardiomyocytes. Ectopic overexpression of GADD153 resulted in the downregulation of CARP expression. Accordingly, the induction of GADD153 mRNA were followed by the CARP down-regulation in an in vivo rat coronary ischemia/reperfusion injury model. These results suggest that GADD153 over-expression and the resulting downregulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.
