Abstract
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.
Highlights
Ethanol is known to induce neurocognitive deficits and to provoke neuronal injuries associated with neuronal degeneration (Givens et al, 2000)
We analyzed the time-course of the effects of subtoxic ethanol exposure (0.1%) on the expression of different genes encoding for antioxidant enzymes with relevant activity in neuronal cells
Our present results demonstrate that treatment of hippocampal HT22 cells with sub-toxic doses of ethanol modifies the expression of specific genes within the classical, thioredoxin, and glutathione systems
Summary
Ethanol is known to induce neurocognitive deficits and to provoke neuronal injuries associated with neuronal degeneration (Givens et al, 2000). It is known that high or chronic ethanol exposure results in the depletion of reduced glutathione (GSH) levels, decreases antioxidant activity, and elevates malondialdehyde and hydroxynonenal protein adducts (Das and Vasudevan, 2007). These increased levels of oxidative stress (and secondary membrane lipid peroxidation, in particular) may disrupt neuronal energy metabolism and ion homeostasis by impairing the function of membrane ion-motive ATPases and glucose and glutamate transporters. The primary mechanism by which ethanol inhibits LTP is the increase in GABAergic transmission, which, in turn, inhibits the depolarization phase required for N-methylD-aspartate (NMDA) receptor activation (White et al, 2000; Schummers and Browning, 2001)
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