Induction of oxidative stress by iron exposure in Hep3B cells as a β-Thalassemia model

抄録

Iron ion is an essential element involved in various metabolic processes including oxygen transport, DNA synthesis, and energy transduction. Excess iron due to the defect of iron balance in a disease such as β-thalassemia, activates nuclear factor-erythroid 2-related factor 2 (Nrf2) and induces the expression of Nrf2 target genes. Nrf2 is a transcription factor responsible for the regulation of cellular oxidative response in mammals. The activation of Nrf2 by excess iron ion is mediated by reactive oxygen species (ROS) formation, which can lead to the induction of oxidative stress. Therefore, efforts to prevent oxidative stress caused by excess iron ion are necessary. In this study, we aimed to investigate the effects of iron chelators on iron ion-induced oxidative stress. We confirmed that exposure of excess iron ion to Hep3B cells for 12 hours increased intracellular ROS and Nrf2 levels, indicating the elevation of oxidative stress. It also upregulated the expression of Nrf2 target genes, such as heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and heavy metal-binding proteins, such as metallothionein (MT) I and II. Next, we treated the Hep3B cell with iron chelator (2,2'-Dipyridyl) for 6 hours under the exposure of iron ion. As expected, dipyridyl diminished the induction effect of iron ion on Nrf2 levels and NQO1 expression. Interestingly, the expression of HO-1, MT-I, and MT-II was induced by dipyridyl treatment. We are now investigating the mechanism underlying elevated HO-1, MT-I, and MT-II expression by dipyridyl under the exposure of iron ion.