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Addition of docosahexaenoic acid (DHA), but not arachidonic acid (ARA), activates glutathione and thioredoxin antioxidant systems in murine hippocampal HT22 cells: potential implications in neuroprotection.
MedLine Citation:
PMID:  25060706     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Docosahexaenoic acid (DHA, 22:6n-3) is a major constituent of nerve cell membrane phospholipids. Besides a role in membrane architecture, DHA is a pleiotropic molecule involved in multiple facets of neuronal biology and also in neuroprotection. We show here that supplementation with DHA (but not arachidonic acid) to mouse hippocampal HT22 cells modulates the expression of genes encoding for antioxidant proteins associated with thioredoxin/peroxiredoxin and glutathione/glutaredoxin systems. Thus, within the thioredoxin system, DHA increased Txn1-2, Trxrd1-2, Prdx3 and Srxn1 gene expression. Paralleling these changes, DHA increased thioredoxin reductase activity, the main enzyme involved in thioredoxin regeneration. For the glutathione system, the most important change triggered by DHA was the upregulation of Gpx4 gene, encoding for the nuclear, cytosolic and mitochondrial isoforms of phospholipid-hydroperoxide glutathione peroxidase (PH-GPx/GPx4, the main enzyme protecting cell membranes against lipid peroxidation), which was followed by a significant increase in total glutathione peroxidase and GPx4 activities. Noticeably, DHA also upregulated a new Gpx4 splicing variant that retained part of the first intronic region. Finally, we demonstrate that DHA treatment, under the same time-course, protects HT22 cells from the oxitoxic exposure to amyloid beta (Aβ25-35 ) peptide. Altogether, our data pinpoint to a role of DHA as Indirect Antioxidant that modulates neuronal defenses in neuroprotection. This article is protected by copyright. All rights reserved.
Authors:
Verónica Casañas-Sánchez; José A Pérez; Noemí Fabelo; Antonio V Herrera-Herrera; Cecilia Fernández; Raquel Marín; María C González-Montelongo; Mario Díaz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-24
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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