Zinc and the modulation of Nrf2 in human neuroblastoma cells.

Zinc and the modulation of Nrf2 in human neuroblastoma cells. Free Radic Biol Med. 2020 May 13;: Authors: Kaufman Z, Salvador GA, Liu X, Oteiza PI Abstract Zinc plays a key role in the modulation of neuronal redox homeostasis. A decreased zinc availability is associated with neuronal NADPH oxidase and nitric oxide synthase activation, deregulation of redox signaling, and impaired glutathione synthesis. The present work tested the hypothesis that zinc is necessary in the neuronal defense response against dopamine (DA)-induced oxidative stress, in particular through heme oxygenase-1 (HO-1) upregulation. DA showed higher cytotoxicity when zinc availability was low. Human IMR-32 neuroblastoma cells responded to high DA concentrations (100 μM) by upregulating HO-1. This upregulation involved Nrf2 translocation to the nucleus, degradation of the Bach-1 repressor, and Nrf2-DNA binding, but it was independent of ERK1/2 activation. DA-mediated induction of HO-1 expression was dependent on the concentration of zinc in the medium. IMR-32 cells incubated in zinc deficient medium showed an impaired response to DA, with lower HO-1 mRNA and protein levels than control DA-challenged cells. This altered HO-1 upregulation was reversed by zinc supplementation. In the presence of DA, Nrf2 nuclear translocation and Bach-1 degradation were lower in zinc deficient cells. The mechanisms involved include: i) impaired Nrf2-tubulin interactions and ii) al...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research