Cap-independent protein translation is initially responsible for 4-(N-methylnitrosamino)-1-(3-pyridyl)-butanone (NNK)-induced apoptosis in normal human bronchial pithelial cells.
- Author:
Seo Hyun MOON
1
;
Hyun Woo KIM
;
Jun Sung KIM
;
Jin Hong PARK
;
Hwa KIM
;
Gook Jong EU
;
Hyun Sun CHO
;
Ga Mi KANG
;
Kee Ho LEE
;
Myung Haing CHO
Author Information
1. Lab of Toxicology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. mchotox@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Cap-dependent protein translation;
NNK;
Apoptosis
- MeSH:
Antibiotics, Antineoplastic/pharmacology;
Apoptosis/*drug effects;
Apoptotic Protease-Activating Factor 1;
BH3 Interacting Domain Death Agonist Protein;
Blotting, Western;
Bronchi/metabolism/*pathology;
Carcinogens/*pharmacology;
Carrier Proteins/metabolism;
Caspases/metabolism;
Cytochromes c/metabolism;
Dose-Response Relationship, Drug;
Epithelial Cells/metabolism/*pathology;
Eukaryotic Initiation Factor-4E/metabolism;
Flow Cytometry;
Humans;
Nitrosamines/*pharmacology;
Protein Biosynthesis;
Proteins/metabolism;
Proto-Oncogene Proteins c-bcl-2/metabolism;
RNA Cap-Binding Proteins/*physiology;
Sirolimus/pharmacology;
Time Factors;
bcl-2-Associated X Protein
- From:Journal of Veterinary Science
2004;5(4):369-378
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 time-dependent 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 pplicable as the mechanical basis of lung cancer treatment.
