期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 48, 期 7, 页码 961-968出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.01.019
关键词
Iron; Zinc; Caco-2 cells; Oxidative stress; Iron signaling; Apoptosis; Iron regulatory protein 1; Free radicals
资金
- Department of Biotechnology
- Government of India
- Indian Council of Medical Research, Government of India [BT/PR6728/AGR/02/334/2005]
Studies in humans and animals have suggested negative interactions of iron and zinc during their intestinal absorption. Further, zinc seems to prevent iron-induced oxidative damage in rats, which was hypothesized to be through the modulation of the intracellular iron signaling pathway. The aim of this study was, therefore, to understand the effects of zinc on oxidant-induced iron signaling and cell death in human enterocyte-like Caco-2 cells. We demonstrate that zinc decreases glucose/glucose oxidase (H2O2-generating system)-induced iron uptake and inhibits iron-regulatory protein 1 activation and divalent metal ion transporter 1 expression. There was also a concomitant decrease in oxidant-induced intracellular labile iron and restoration of ferritin and metallothionein expression. Further, zinc enhanced the Bcl-2/Bax ratio and reduced caspase-3 activity, leading to inhibition of apoptosis. Interestingly, bathophenanthroline disulfonic acid, an extracellular iron chelator, emulated the effects of zinc except for the reduced ferritin levels. These results suggest that zinc inhibits apoptosis by reducing oxidant-induced iron signaling in Caco-2 cells. (C) 2010 Elsevier Inc. All rights reserved.
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