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

J Vet Sci. 2004 Dec;5(4):369-78.

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 applicable as the mechanical basis of lung cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects*
  • Apoptotic Protease-Activating Factor 1
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Western
  • Bronchi / metabolism
  • Bronchi / pathology*
  • Carcinogens / pharmacology*
  • Carrier Proteins / metabolism
  • Caspases / metabolism
  • Cytochromes c / metabolism
  • Dose-Response Relationship, Drug
  • Epithelial Cells / metabolism
  • Epithelial Cells / 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

Substances

  • APAF1 protein, human
  • Antibiotics, Antineoplastic
  • Apoptotic Protease-Activating Factor 1
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carcinogens
  • Carrier Proteins
  • Eukaryotic Initiation Factor-4E
  • Nitrosamines
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA Cap-Binding Proteins
  • bcl-2-Associated X Protein
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Cytochromes c
  • Caspases
  • Sirolimus