ABSTRACT
Hyperoxia (fraction of inspired oxygen = 95%) induces death of lung epithelial cells. The duration of cell survival in the setting of hyperoxia depends on hyperoxia-induced activation of intracellular survival pathways. Two survival pathways with known effects on lung epithelial cells are the propidium iodide 3-kinase/Akt and extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase pathways. We investigated the effect of hyperoxia on activity of both the Akt and ERK pathways in the A549 lung epithelial cell line. Hyperoxia-exposed cells show progressive loss of Akt activation and total Akt protein. Hyperoxia decreases Akt mRNA, consistent with the loss of total Akt. In addition, hyperoxia induces ERK activation. Inhibition of ERK with the MAP kinase kinase 1/2 inhibitor, U0126, shortens the survival time of cells in hyperoxia, suggesting that increased ERK activity partially compensates for the hyperoxia-induced Akt downregulation. Our findings show, for the first time, that hyperoxia has divergent effects on two survival pathways (Akt and ERK), and that ERK activity compensates for the loss of the Akt survival effects, delaying the death of hyperoxia-exposed lung epithelial cells.
Subject(s)
Down-Regulation/drug effects , Epithelial Cells/cytology , Epithelial Cells/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Oxygen/pharmacology , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Apoptosis/drug effects , Caspase Inhibitors , Caspases/metabolism , Cell Death/drug effects , Cell Line , Cell Nucleus/pathology , Enzyme Activation/drug effects , Epithelial Cells/enzymology , Epithelial Cells/metabolism , Humans , Lung/cytology , Necrosis/chemically induced , Poly(ADP-ribose) Polymerases/metabolism , Propidium/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-akt , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Chronic care facility stay has been shown to be an independent risk factor for venous thromboembolism. Review of the literature, however, reveals a paucity of data addressing the issue of venous thromboembolism in nursing home residents. The purpose of this study was to determine the incidence of venous thromboembolic events among nursing home residents. A retrospective cohort study was derived from data compiled in the State of Kansas Minimum Data Set (MDS) for nursing home residents from July 1, 1997 to July 1, 1998. A total of 18,661 residents (median age, 85 years, 74% female, 95% white) satisfied the study criteria. The outcome measures of the primary endpoint-development of a venous thromboembolic event (VTE)-were obtained from the MDS quarterly health assessments and the Medicare ICD-9 codes. We determined the incidence of VTE among nursing home residents as 1.30 events per 100 person-years of observation.
