Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species.
- Author:
Bo Yeon PARK
1
;
Jayong CHUNG
Author Information
- Publication Type:Original Article
- Keywords: Iron; cadmium; ferroportin 1; macrophages
- MeSH: Animals; Cadmium; Cation Transport Proteins; Gene Expression; Hand; Homeostasis; Iron; Luciferases; Macrophages; Mice; Reactive Oxygen Species; RNA, Messenger
- From:Nutrition Research and Practice 2009;3(3):192-199
- CountryRepublic of Korea
- Language:English
- Abstract: Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism.
