Zinc inhibits oxidative stress-induced iron signaling and apoptosis in Caco-2 cells.
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 (H(2)O(2)-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.
Kilari
Sreenivasulu
S
National Institute of Nutrition, Jamai Osmania, Hyderabad, India.
Pullakhandam
Raghu
R
Nair
K Madhavan
KM
D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D002614:Chelating Agents / Q000494:pharmacology; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010618:Phenanthrolines / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015032:Zinc / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
D053148:Caspase 3; D027682:Cation Transport Proteins; D002614:Chelating Agents; D005293:Ferritins; D007501:Iron; D035925:Iron-Regulatory Proteins; D008668:Metallothionein; D010618:Phenanthrolines; D019253:Proto-Oncogene Proteins c-bcl-2; D015032:Zinc; D051028:bcl-2-Associated X Protein; D000099236:Solute Carrier Family 11, Member 2; C017049:bathophenanthroline disulfonic acid