title: Upregulation of haeme oxygenase-1 by zinc in HCT-116 cells.
abstract: Haeme oxygenase-1 (HO-1) is often viewed as a cytoprotective gene. Toxic heavy metals induce HO-1, but it is unclear whether particular metal micronutrients also induce HO-1. Hence, the ability of exogenously-added copper, iron and zinc to influence HO-1 expression in HCT-116 cells was evaluated. Under the chosen experimental conditions, only zinc noticeably increased the expression of HO-1 mRNA and protein. Concurrently, zinc decreased non-protein thiol levels to a certain extent, but zinc did not increase the production of reactive oxygen species (ROS). Moreover, ascorbate and Trolox did not inhibit zinc-induced HO-1 upregulation. In contrast, deferoxamine blunted the induction of HO-1 mRNA, protein, and enzymatic activity caused by zinc. Additionally, N-acetylcysteine and Tiron inhibited zinc-induced HO-1 upregulation and also nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Collectively, these findings suggest that zinc at above normal levels upregulates HO-1 expression in HCT-116 cells in a ROS-independent manner.
authors.affiliation: Cellular and Molecular Nutrition Research Laboratory, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA.
authors.forename: Abigail F
authors.initials: AF
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Loo
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D045325:HCT116 Cells; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D015032:Zinc