title: Inhibition of lung epithelial cell proliferation by hyperoxia. Posttranscriptional regulation of proliferation-related genes.
abstract: The alveolar surface of the lung is a major target for oxidant injury. After injury, repair of the alveolar epithelium is dependent on the ability of epithelial type 2 (T2) cells to proliferate. The regulation of T2 cell proliferation and the effect of reactive oxygen (O2) species on this lung cell proliferation have not been well defined. To investigate this process we focused on the regulation of two late cell cycle genes, histone and thymidine kinase, in T2 cells and fibroblasts exposed in vitro to varying periods of hyperoxia (95% O2). Hyperoxia for 24 to 48 h arrested cell proliferation in a SV40T-immortalized T2 cell line we have developed and in primary and SV40T-immortalized lung fibroblasts. Despite the cessation of proliferation, histone and TK mRNA continued to be expressed at high levels; mRNA half-lives were markedly prolonged but neither protein was translated. Thus proliferation arrest induced by hyperoxia was associated with posttranscriptional control of at least two late cell cycle-related genes. This form of proliferation arrest is also seen when primary and SV40T-T2 cells but not fibroblasts are serum deprived, suggesting that T2 cells in vitro may be uniquely sensitive to alterations in their redox state and that these alterations in turn affect translational control of a subset of proliferation-related genes.
authors.affiliation: Physiology Department, Hôpital Trousseau, St. Antoine Medical School, University of Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Clement
authors.forename: M
authors.initials: M
authors.lastname: Edeas
authors.forename: K
authors.initials: K
authors.lastname: Chadelat
authors.forename: J S
authors.initials: JS
authors.lastname: Brody
mesh_terms: D000818:Animals; D002455:Cell Division; D015687:Cell Hypoxia; D002460:Cell Line; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D012333:RNA, Messenger; D013937:Thymidine Kinase