Cited 10 times in

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

Title
Protective effect of survivin in Doxorubicin-induced cell death in h9c2 cardiac myocytes.
Authors
Beom Seob Lee;Soo Hyuk Kim;Seok-Min Kang;Ji Hyung Chung;Sang Hak Lee;Sungha Park;Jaewon Oh;Eun Young Choi;Taewon Jin
Issue Date
2013
Journal Title
Korean Circulation Journal (순환기)
ISSN
1738-5520
Citation
Korean Circulation Journal (순환기), Vol.43(6) : 400~407, 2013
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.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/88400
DOI
10.4070/kcj.2013.43.6.400
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Cardiovascular Product Evaluation Center
Yonsei Authors
사서에게 알리기
  feedback
Files in This Item:
T201303949.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse