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Protective effect of survivin in Doxorubicin-induced cell death in h9c2 cardiac myocytes.

Authors
 Beom Seob Lee  ;  Soo Hyuk Kim  ;  Taewon Jin  ;  Eun Young Choi  ;  Jaewon Oh  ;  Sungha Park  ;  Sang Hak Lee  ;  Ji Hyung Chung  ;  Seok-Min Kang 
Citation
 KOREAN CIRCULATION JOURNAL, Vol.43(6) : 400-407, 2013 
Journal Title
KOREAN CIRCULATION JOURNAL
ISSN
 1738-5520 
Issue Date
2013
Keywords
Apoptosis ; Doxorubicin ; Myocytes, cardiac
Abstract
BACKGROUND AND OBJECTIVES:
Apoptosis has been known to be an important mechanism of doxorubicin-induced cardiotoxicity. Survivin, which belongs to the inhibitor of apoptosis protein family, is associated with apoptosis and alteration of the cardiac myocyte molecular pathways. Therefore, we investigated the anti-apoptotic effect and cellular mechanisms of survivin using a protein delivery system in a doxorubicin-induced cardiac myocyte injury model.
MATERIALS AND METHODS:
We constructed a recombinant survivin which was fused to the protein transduction domain derived from HIV-TAT protein. In cultured H9c2 cardiac myocytes, TAT-survivin (1 µM) was added for 1 hour prior to doxorubicin (1 µM) treatment for 24 hours. Cell viability and apoptosis were evaluated by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, caspase-3 activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay. We measured the expression levels of several apoptosis-related signal proteins.
RESULTS:
The survivin level was significantly reduced in a dose dependent manner up to 1 µM of doxorubicin in concentration. Purified recombinant TAT-survivin protein was efficiently delivered to H9c2 cardiac myocytes, and its transduction showed an anti-apoptotic effect, demonstrated by reduced caspase-3 activity and the apoptotic index, concomitantly with increased cell viability against doxorubicin injury. The phosphorylation of p38 mitogen-activated protein (MAP) kinase and the release of Smac from mitochondria were suppressed and the expression levels of Bcl-2 and cAMP response element-binding protein (CREB), the transcription factor of Bcl-2, were recovered following TAT-survivin transduction, indicating that survivin had an anti-apoptotic effect against doxorubicin injury.
CONCLUSION:
Our results suggest that survivin has a potentially cytoprotective effect against doxorubicin-induced cardiac myocyte apoptosis through mechanisms that involve a decrease in the phosphorylation of p38 MAP kinase, mitochondrial Smac release, and increased expression of Bcl-2 and CREB.
Files in This Item:
T201303949.pdf Download
DOI
10.4070/kcj.2013.43.6.400
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Kim, Soo Hyuk(김수혁)
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Beom Seob(이범섭)
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Chung, Ji Hyung(정지형)
Jin, Tae Won(진태원)
Choi, Eun Young(최은영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88400
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