Publication: Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: An insight into the Fas connection
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Issued Date
2006-02-01
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ISSN
15357163
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2-s2.0-33644976426
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Cancer Therapeutics. Vol.5, No.2 (2006), 261-269
Suggested Citation
Yu Chin Lien, Shu Mei Lin, Ramaneeya Nithipongvanitch, Terry D. Oberley, Teresa Noel, Qing Zhao, Chotiros Daosukho, Daret K. St. Clair Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: An insight into the Fas connection. Molecular Cancer Therapeutics. Vol.5, No.2 (2006), 261-269. doi:10.1158/1535-7163.MCT-05-0390 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/23095
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Title
Tumor necrosis factor receptor deficiency exacerbated Adriamycin-induced cardiomyocytes apoptosis: An insight into the Fas connection
Abstract
Cardiomyopathy is a major dose-limiting factor for applications of Adriamycin, a potent chemotherapeutic agent. The present study tested the hypothesis that increased tumor necrosis factor (TNF)-α signaling via its receptors protects against Adriamycin-induced cardiac injury. We used mice in which both TNF receptor I and II have been selectively inactivated (DKO) with wild-type mice as controls. Morphometric studies of cardiac tissue following Adriamycin treatment revealed greater ultrastructural damage in cardiomyocyte mitochondria from DKO mice. Biochemical studies of cardiac tissues showed cytochrome c release and the increase in proapoptotic protein levels, suggesting that lack of TNF-α receptor I and II exacerbates Adriamycin-induced cardiac injury. The protective role of TNF receptor I and II was directly confirmed in isolated primary cardiomyocytes. Interestingly, following Adriamycin treatment, the levels of Fas decreased in the wild-type mice. In contrast, DKO mice had an increase in Fas levels and its downstream target, mitochondrial truncated Bid. These results suggested that TNF-α receptors play a critical role in cardioprotection by suppression of the mitochondrial-mediated associated cell death pathway. Copyright © 2006 American Association for Cancer Research.