Heme oxygenase-1 Induction by Exposure to Various Metal Ions: Studies on lnteractions of Minerals by Using a Human Intestinal Cell Culture System

Abstract

Cells respond to metabolic perturbations by inducing specific stress proteins. Exposure of mammalian cells to oxidative stress induces heme oxygenase, the rate-limiting enzyme in heme degradation. The induction of heme oxygenase-1 has been hypothesized to represent a cellular antioxidant defense mechanism. The objectives of this study were to characterize the interaction of minerals in human intestinal epithelial cells (Caco-2 cell line) and to explain the mechanism of heme oxygenase-1 induction by oxidative stress. The induction levels of heme oxygenase-1 depended on chemical forms of iron (hemin > Fe (II) > Fe (III) NTA) in Caco-2. As opposed to hemin, Cu (II) is a weak inducer of heme oxygenase-1. Induction levels of heme oxygenase-1 when Cu (II) coexisted with hemin in the medium was same as when hemin only existed. Although both hemin and arsenate are strong inducers of heme oxygenase-1, the induction level of heme oxygenase-1 when arsenate coexisted with hemin was lower than when hemin or arsenate solely existed. These coexistences of minerals required a lot of time to induce a maximum level of heme oxygenase-1. Although it did not reveal whether generation of hydrogen peroxide by exposure to various minerals in Caco-2 cells initiated to induce heme oxygenase-1, it was demonstrated that hydrogen peroxide remarkably induced heme oxygenase-1. These results suggest dietary minerals affected the mechanism of heme oxygenase-1 induction in intestinal epithelial cells.