Sub-toxic ethanol exposure modulates gene expression and enzyme activity of antioxidant systems to provide neuroprotection in hippocampal HT22 cells

• Main Authors: Veronica Casañas-Sanchez, José Antonio Pérez, David Quinto Alemany, Mario Diaz
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2016-07-01
• Series: Frontiers in Physiology
• Subjects: Ethanol; Glutathione; thioredoxin; Antioxidant systems; Superoxide dismutases; HT22 cells
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00312/full

Ethanol is known to cause severe systemic damage often explained as secondary to oxidative stress. Brain is particularly vulnerable to ethanol-induced reactive oxygen species (ROS) because the high amounts of lipids, and because nerve cell membranes contain high amounts of peroxidable fatty acids. Usually these effects of ethanol are associated to high and/or chronic exposure to ethanol. However, as we show in this manuscript, a low and acute dose of ethanol trigger a completely different response in hippocampal cells. Thus, we have observed that 0.1% ethanol exposure to HT22 cells, a murine hippocampal-derived cell line, increases the transcriptional expression of different genes belonging to the classical, glutathione/glutaredoxin and thioredoxin/peroxiredoxin antioxidant systems, these including Sod1, Sod2, Gpx1, Gclc and Txnrd1. Paralleling these changes, enzyme activities of total superoxide dismutase (tSOD), catalase, total glutathione peroxidase (tGPx), glutathione-S-reductase (GSR) and total thioredoxin reductase (tTXNRD), were all increased, while the generation of thiobarbituric acid reactive substances (TBARS), as indicators of lipid peroxidation, and glutathione levels remained unaltered. Ethanol exposure did not affect cell viability or cell growing as assessed by real-time cell culture monitoring, indicating that low ethanol doses are not deleterious for hippocampal cells, but rather prevented glutamate-induced excitotoxicity. In summary, we conclude that sub-toxic exposure to ethanol may well be neuroprotective against oxidative insults in hippocampal cells.