KMID : 0368120080380050264
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Korean Circulation Journal 2008 Volume.38 No. 5 p.264 ~ p.269
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Effects of Cardiotrophin-1 on Adriamycin-Induced Apoptosis in H9c2 Cardiomyoblasts
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Shin Jae-Ok
Ju Eun-Seon Song Hyun-Mi Yun Soo-Hyeon Lim Byung-Kwan Choi Jin-Ho Kim Duk-Kyung Jeon Eun-Seok
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Abstract
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Background and Objectives: Adriamycin (doxorubicin, ADR) is a highly effective anti-neoplastic drug, but its clinical use is limited by its adverse side effects on the heart. Cardiotrophin (CT-1), a potent cardiac survival factor, is capable of inhibiting apoptosis in cardiac myocytes. The aim of this study was to investigate the cyto-protective effects of CT-1 against ADR-induced apoptosis in vitro.
Subjects and Methods: We determined a reasonable ADR concentration for inducing cell death by utilizing a cell survival test performed in a dose-dependent manner. To determine the requirements for apoptosis in ADR-treated cardiac myocytes (H9c2 cells), we examined the effect of CT-1 on survival and apoptotic changes using a cell counting kit (CCK), RT-PCR, and Western blotting.
Results: In analyzing cell survival as determined by CCK, ADR-induced cell death was found to occur in a dose-dependent manner (50% death at 24 hours after 2 ¥ìM of ADR), and ADR was shown to decrease procaspase-3. On RT-PCR, expression of Bax-¥á mRNA increased and Bcl-2 decreased during the 24 hours after ADR treatment. Consequently, the ratio of Bax-¥á/Bcl-2 mRNA peaked at 24 hours after ADR treatment. In contrast, CT-1 effectively attenuated the ADR-induced cell death in a dose-dependent manner. The changes in Bax-¥á and Bcl-2 mRNA expression after ADR treatment were reversed by CT-1 (1 ng/mL) treatment. The protein levels of procaspase-3 decreased after ADR treatment, an effect which was reversed by CT-1 treatment. Akt phosphorylation was also increased by CT-1, demonstrating that CT-1 inhibited apoptosis induced by ADR.
Conclusion: These data demonstrated that ADR-induced apoptosis of cardiomyocytes can be prevented by CT-1; therefore, it may be possible to use CT-1 as a cardioprotective agent during ADR chemotherapy in patients with cancer.
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KEYWORD
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Adriamycin, Cardiotrophin-1, Apoptosis, Cell protection
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