Zinc modulates the neuronal response to dopamine-induced oxidative stress.

SALVADOR, G; OMATA, YO; NUTALL, J; SUANGSUDA, S; OTEIZA, P

Kioto

Congreso; International Meeting the Society for Free Radical Biology and Medicine.; 2014

Society for Free Radical Biology and Medicine.

Zinc modulates the neuronal response to dopamine-induced oxidative stress. Salvador, G., Omata, Y., Supasai, S. Nutall, J, and Oteiza, P.I.1Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET). Bahía Blanca, Argentina2,3Departments of 2Nutrition and 3Environmental Toxicology, University of California, Davis, USA.Zinc (Zn) plays a key role in the modulation of neuronal redox status. The present work tested the hypothesis that Zn is necessary in the neuronal defense response against dopamine (DA)-induced oxidative stress. Human IMR-32 neuroblastoma cells exposed to high DA (100 µM) under a condition of Zn deficiency (ZD) showed an impaired capacity to upregulate hemooxigenase (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC) mRNA and protein levels. This was reverted by Zn supplementation. ZD decreased de capacity of IMR-32 cells to upregulate Nrf-2 and ERK1/2 as a protective response against DA. Supplementation of ZD cells with lipoic acid (LA) restored DA-induced GCLC expression and Nrf-2 activation, but not HO-1 expression and ERK1/2 activation compared to Zn sufficient cells. Restoration of ERK1/2 activity was independent of redox dependent mechanisms. Results show that Zn is necessary for the neuronal protective response against DA damage. LA supplementation can only restore redox-dependent mechanisms when Zn availability is low.