Pro-apoptotic role of nuclear factor-κB in adriamycin-induced acute             myocardial injury in rats.
Nuclear factor κB (NF-κB) is activated by a wide range of inducers and is able to mediate gene transcription. We investigated the role of NF-κB in adriamycin-induced myocardial injury in rats and its mechanism of action. A total of 30 male Wistar rats were randomly divided into 3 groups: control, anthracycline antibiotic adriamycin (ADR) and ADR + pyrrolidine dithiocarbamate (PDTC). Myocardial apoptosis was detected by TUNEL assay; myocardium p53 gene expression was examined by RT-PCR analysis; location and distribution of p53 was observed by immunohistochemical assay; myocardial expression of p53 protein was assessed by Western blot analysis and activity of NF-κB was evaluated by electrophoretic mobility shift assay. The binding activity of NF-κB, myocardial apoptotic index and expression of p53 increased significantly in the ADR groups. All of these changes induced by ADR were inhibited by PDTC. It was concluded that NF-κB activation may be pro-apoptotic through regulation of the expression of p53 in adriamycin-induced myocardial injury.
Department of Cardiology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, PR China.
Fang
F
Wang
Hongli
H
Li
Haoying
H
Shi
Baogui
B
Sun
D000208:Acute Disease; D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis; D004249:DNA Damage; D004317:Doxorubicin; D005786:Gene Expression Regulation / Q000187:drug effects; D006335:Heart Injuries / Q000139:chemically induced*; D020287:In Situ Nick-End Labeling; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin