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J. Biol. Chem., Vol. 280, Issue 24, 23122-23129, June 17, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/24/23122    most recent M501095200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Han, X.-J. Articles by Kim, D.-G. Search for Related Content PubMed PubMed Citation Articles by Han, X.-J. Articles by Kim, D.-G. Social Bookmarking                      What's this?

Involvement of GADD153 and Cardiac Ankyrin Repeat Protein in Hypoxia-induced Apoptosis of H9c2 Cells^*

Xue-Ji Han, Jei-Keon Chae, Mi-Jin Lee, Kyung-Ran You, Byung-Ho Lee¶, and Dae-Ghon Kim||

From the Divisions of Hepatology and Cardiology, Department of Internal Medicine, the Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, South Korea and the ^¶Korea Research Institute of Chemical Technology, Yusong, Taejon 305-600, South Korea

Oxidative stress is the main cause of cardiac injury during ischemia/reperfusion but the molecular mechanism for this process is unclear. In this study, it was found that hypoxia induces apoptosis in rat embryonic heart-derived H9c2 cells leading to the induction of GADD153, which is an apoptosis-related gene. Therefore, this study addressed the molecular role of GADD153 in hypoxia-induced apoptosis. The stable or inducible overexpression of GADD153 sensitized the H9c2 cells to apoptotic cell death. The results suggest that the transactivation domain of the GADD153 might be responsible for this cell execution and play a role in the nucleoplasmic localization of GADD153. The cells transiently transfected with the antisense GADD153 were more resistant to hypoxia-induced apoptosis than the vector control cells. Furthermore, GADD153 transcriptionally down-regulated the expression of the cardiac ankyrin repeat protein gene (CARP), which is a nuclear transcriptional co-factor that negatively regulates the expression of the cardiac gene. The ectopic expression of CARP in H9c2 cells increased the resistance to hypoxia-induced apoptosis. These results suggest that GADD153 overexpression and the concomitant down-regulation of CARP might have a causative role in the apoptotic cell injury of hypoxic H9c2 cells.

Received for publication, January 31, 2005 , and in revised form, April 4, 2005.

^* This work was supported in part by Grant FG03-11-01 (to D.-G. K.) from the 21C Frontier Human Genome Project, The Ministry of Science and Technology, Republic of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Division of Gastroenterology and Hepatology, Dept. of Internal Medicine, The Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, 634-18 Keumam-dong, Dukjin-ku, Jeonju, Jeonbuk 561-172, South Korea. Tel.: 82-63-250-1681; Fax: 82-63-254-1609; E-mail: daeghon{at}chonbuk.ac.kr.

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