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Báo cáo khoa học: " Cap-independent protein translation is initially responsible for 4-(N-methylnitrosamino)-1-(3-pyridyl)-butanone (NNK)-induced apoptosis in normal human bronchial pithelial cells"

Tuyển tập các báo cáo nghiên cứu khoa học quốc tế về bệnh thú y đề tài: Cap-independent protein translation is initially responsible for 4-(N-methylnitrosamino)-1-(3-pyridyl)-butanone (NNK)-induced apoptosis in normal human bronchial pithelial cells | J. Vet. Sci. 2004 5 4 369-378 JOURNAL OF Veterinary Science Cap-independent protein translation is initially responsible for 4- N-methylnitrosamino -1- 3-pyridyl -butanone NNK -induced apoptosis in normal human bronchial epithelial cells Seo-Hyun Moon1 Hyun-Woo Kim1 Jun-Sung Kim1 Jin-Hong Park1 Hwa Kim1 Gook-Jong Eu1 Hyun-Sun Cho1 Ga-Mi Kang1 Kee-Ho Lee2 Myung-Haing Cho lLab of Toxicology College of Veterinary Medicine and School of Agricultural Biotechnology Seoul National University Seoul 151-742 Korea 2Lab of Molecular Oncology Korea Institute of Radiological Medical Sciences Seoul 130-706 Korea Evidences show that eukaryotic mRNAs can perform protein translation through internal ribosome entry sites IRES . 5 -Untranslated region of the mRNA encoding apoptotic protease-activating factor 1 Apaf-1 contains IRES and thus can be translated in a cap-independent manner. Effects of changes in protein translation pattern through rapamycin pretreatment on 4- methylnitrosamino -1- 3-pyridyl -butanone NNK tobacco-specific lung carcinogen -induced apoptosis in human bronchial epithelial cells were examined by caspase assay FACS analysis Western blotting and transient transfection. Results showed that NNK induced apoptosis in concentration- and timedependent manners. NNK-induced apoptosis occurred initially through cap-independent protein translation which during later stage was replaced by cap-dependent protein translation. Our data may be applicable as the mechanical basis of lung cancer treatment. Key words Cap-dependent protein translation NNK Apoptosis Introduction Protein translation an important step in the cellular protein synthesis of eukaryotic cells is a multiphase process in which each phase that is initiation elongation and termination is affected and regulated by distinct factors 3 7 . In eukaryotic cells different modes of translation initiation are used depending on the nature of mRNA to be translated and physiological state of the cell 10 with two most .