J Vet Sci.  2004 Dec;5(4):369-378.

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

• Moon SH
• Kim HW
• Kim JS
• Park JH
• Kim H
• Eu GJ
• Cho HS
• Kang GM
• Lee KH
• Cho MH

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.

Keyword

Cap-dependent protein translation; NNK; Apoptosis

MeSH Terms

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