Involvement of redox events in caspase activation in zinc-depleted airway epithelial cells |
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Authors: | Carter Joanne E Truong-Tran Ai Q Grosser Dion Ho Lien Ruffin Richard E Zalewski Peter D |
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Institution: | Department of Medicine, Adelaide University, The Queen Elizabeth Hospital, Woodville 5011, Australia. |
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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 Zn(2+), a cellular regulator of pro-caspase-3, in primary sheep and human AEC. Zn(2+) 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 Zn(2+) in sheep AEC, using the membrane permeant Zn(2+) 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 Zn(2+) and other anti-oxidants. |
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Keywords: | Zinc Caspase-3 Cu/Zn SOD N-acetylcysteine Airway epithelium Basal bodies Zinquin Lipid peroxidation Anti-oxidant |
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