Adriamycin induces myocardium apoptosis through activation of nuclear factor κB in rat

被引:29
作者
Li, Shufeng [1 ]
E, Mingyan [2 ]
Yu, Bo [1 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China
[2] Harbin Med Univ, Affiliated Tumor Hosp, Dept Radiotherapy, Harbin 150086, Peoples R China
关键词
Adriamycin; Nuclear factor-kappa B; Myocardium; Apoptosis;
D O I
10.1007/s11033-007-9112-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Adriamycin is one of the most effective and useful antineoplastic agents. Acute doxorubicin cardiotoxicity involved cardiomyocyte apoptosis. In this study, we investigated whether adriamycin induced myocardium apoptosis through activation of nuclear factor kappa B in rat. Forty male Wistar rats were randomly divided into five groups: control, ADR 5 mg/kg, ADR 10 mg/kg, ADR 15 mg/kg group and ADR + PDTC 200 mg/ml group. Myocardial apoptosis was detected by DNA fragmentation assay and TUNEL assay; Location and distribution of p-I kappa B alpha was observed by immunohistochemical assay; Myocardial expression of p-I kappa B alpha protein was assessed by Western blot analysis; Activity of NF-kappa B was evaluated by Electrophoretic Mobility Shift Assay. The myocardial apoptotic index, expression of p-I kappa B alpha, and binding activity of NF-kappa B increased significantly in ADR groups in dose-dependent manner. PDTC as a nonspecific inhibitor of NF-kappa B protected myocardium from apoptosis by inhibiting NF-kappa B activation. Adriamycin induces myocardium apoptosis through activation of nuclear factor kappa B in rat and NF-kappa B activation requires I kappa B alpha degradation.
引用
收藏
页码:489 / 494
页数:6
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