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|Title:||Involvement of redox events in caspase activation in zinc-depleted airway epithelial cells|
|Citation:||Biochemical and Biophysical Research Communications, 2002; 297(4):1062-1070|
|Publisher:||Academic Press Inc|
|Joanne E. Carter, Ai Q. Truong-Tran, Dion Grosser, Lien Ho, Richard E. Ruffin and Peter D. Zalewski|
|Abstract:||Airway epithelial cells (AEC) contain both pro- and anti-apoptotic factors but little is known about mechanisms regulating apoptosis of these cells. In this study we have examined the localization of pro-caspase-3 and Zn2+, a cellular regulator of pro-caspase-3, in primary sheep and human AEC. Zn2+ was concentrated in both cytoplasmic vesicles and ciliary basal bodies, in the vicinity of both pro-caspase-3 and the antioxidant Cu/Zn superoxide dismutase (Cu/Zn SOD). Depletion of intracellular Zn2+ in sheep AEC, using the membrane permeant Zn2+ chelator TPEN, increased lipid peroxidation in the apical cell membranes (as assessed by immunofluorescence with anti-hydroxynonenal) as well as increasing activated pro-caspase-3 and apoptosis. There were smaller increases in caspase-2 and -6 but not other caspases. Activation of caspase-3 in TPEN-treated AEC was inhibited strongly by N-acetylcysteine and partially by vitamin C and vitamin E. These findings suggest that cytoplasmic pro-caspase-3 is positioned near the lumenal surface of AEC where it is under the influence of Zn2+ and other anti-oxidants.|
|Keywords:||Zinc; Caspase-3; Cu/Zn SOD; N-acetylcysteine; Airway epithelium; Basal bodies; Zinquin; Lipid peroxidation; Anti-oxidant|
|Description:||Copyright © 2002 Elsevier Science (USA). All rights reserved.|
|Appears in Collections:||Medicine publications|
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