학술논문
Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice.
Document Type
Academic Journal
Author
Díaz M; Department of Physics, Faculty of Sciences, University of La Laguna, 38200 Tenerife, Spain.; Instituto Universitario de Neurociencias (IUNE), University of La Laguna, 38320 Tenerife, Spain.; Valdés-Baizabal C; Instituto Universitario de Neurociencias (IUNE), University of La Laguna, 38320 Tenerife, Spain.; Laboratory of Cellular Neurobiology, Department of Basic Medical Sciences, Faculty of Health Sciences, University of La Laguna, 38200 Tenerife, Spain.; de Pablo DP; Instituto Universitario de Neurociencias (IUNE), University of La Laguna, 38320 Tenerife, Spain.; Laboratory of Cellular Neurobiology, Department of Basic Medical Sciences, Faculty of Health Sciences, University of La Laguna, 38200 Tenerife, Spain.; Marin R; Instituto Universitario de Neurociencias (IUNE), University of La Laguna, 38320 Tenerife, Spain.; Laboratory of Cellular Neurobiology, Department of Basic Medical Sciences, Faculty of Health Sciences, University of La Laguna, 38200 Tenerife, Spain.; Associate Research Unit ULL-CSIC 'Membrane Physiology and Biophysics in Neurodegenerative and Cancer Diseases', 38200 Tenerife, Spain.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2076-3921
Abstract
The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer's disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a "rejuvenation" of hippocampal antioxidant defense.