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Neutral endopeptidase of a human airway epithelial cell line recovers after hypochlorous acid exposure: dexamethasone accelerates this by stimulating neutral endopeptidase mRNA synthesis.
Am J Respir Cell Mol Biol 1992 Sep; 7(3):300-306
A study was conducted to evaluate the activity of neutral- endopeptidase-24.11 (NEP) in the human airway epithelial cell line Calu-1 after exposure to hypochlorous-acid (7790923) (HOCl), and to determine the influence of glucocorticoid treatment on this reaction. Calu-1 cells were cultured and exposed to 100 micromolar (microM) HOCl for 5 minutes; some cells were cooled to 4 degrees-C and preincubated with 1 millimolar sodium-azide (26628228) for 5 minutes prior to HOCl exposure. For studies on post HOCl recovery, cells were kept in culture for 48 hours either with or without the presence of dexamethasone. NEP activity and cleavage products were assessed via high performance liquid chromatography. NEP specific mRNA was assessed using Northern blot analysis. NEP activity was decreased to about 70% of preexposure levels after a 5 minute exposure to HOCl. At 4 degrees-C, sodium-azide was found to block the effect of HOCl on Calu-1 NEP. In trials without sodium-azide, NEP activity was found to return to preexposure levels within 24 hours. In the presence of 1microM dexamethasone, this recovery occurred 6 hours earlier; dexamethasone was also found to increase NEP activity at 24 and 48 hours after HOCl. NEP specific mRNA did not change during the recovery period as indicated by Northern analysis, but was increased 44 to 50% by dexamethasone 24 hours after HOCl. The authors conclude that HOCl exposure decreases plasma membrane NEP in Calu-1 cells by inducing its internalization, and that internalized enzyme exocytosis may be responsible for the spontaneous recovery of cell surface NEP. The authors also suggest that dexamethasone treatment, which stimulates NEP specific mRNA synthesis in these cells, can substantially accelerate recovery.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Acids; Enzyme-activity; Cell-cultures; Toxic-effects; In-vitro-studies; Cytotoxic-effects; Cellular-reactions; Mammalian-cells
Christopher Murlas, M.D., Department of Medicine (Pulmonary and Critical Care Medicine), Rush University, 1653 W. Congress Parkway, Chicago, IL 60612
Issue of Publication
American Journal of Respiratory Cell and Molecular Biology
Rush-Presbyterian St. Luke Medical Center, Department of Medicine (Pulmonary), Chicago, IL 60612
Page last reviewed: April 12, 2019
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