Differential induction of c-fos, c-jun, and apoptosis in lung epithelial cells exposed to ROS or RNS.
Reactive oxygen (ROS) or nitrogen (RNS) species can affect epithelial cells to cause acute damage and an array of pulmonary diseases. The goal of this study was to determine patterns of early response gene expression and functional end points of exposure to nitric oxide (NO.), H2O2, or peroxynitrite (ONOO-) in a line of rat lung epithelial (RLE) cells. Our focus was on c-fos and c-jun protooncogenes, as these genes play an important role in proliferation or apoptosis, possible end points of exposure to reactive metabolites in lung. Our data demonstrate that NO. generated by spermine 1,3-propanediamine N-14-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]-butyl] or S-nitroso-N-acetylpenicillamine as well as H2O2 cause increased c-fos and c-jun mRNA levels, nuclear proteins, and complexes binding the activator protein-1 recognition sequence in RLE cells. These agents also lead to apoptosis and increased membrane permeability. In contrast, exogenously administered ONOO- or 3-morpholinosydnonimine do not induce protooncogenes or apoptosis in RLE cells despite nitration oftyrosines. We conclude that ROS and RNS can elicit distinct molecular and phenotypic responses in a target cell of pulmonary disease.
Janssen
Y M
YM
Department of Pathology, University of Vermont, Burlington 05405, USA.
Matalon
S
S
Mossman
B T
BT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species; D026423:S-Nitroso-N-Acetylpenicillamine; D013096:Spermine / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D009566:Nitrates; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C039642:peroxynitric acid; D013096:Spermine; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D006861:Hydrogen Peroxide; D008981:Molsidomine; D010396:Penicillamine