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Short-chain C2 ceramide induces heme oxygenase-1 expression by upregulating AMPK and MAPK signaling pathways in rat primary astrocytes

Title
Short-chain C2 ceramide induces heme oxygenase-1 expression by upregulating AMPK and MAPK signaling pathways in rat primary astrocytes
Authors
Jung J.-S.Choi M.-J.Ko H.-M.Kim H.-S.
Ewha Authors
김희선고현명
SCOPUS Author ID
김희선scopus
Issue Date
2016
Journal Title
Neurochemistry International
ISSN
0197-0186JCR Link
Citation
vol. 94, pp. 39 - 47
Keywords
AstrocyteC2 ceramideHeme oxygenase-1Oxidative stressPhase II antioxidant enzymeSignaling mechanism
Publisher
Elsevier Ltd
Indexed
SCI; SCIE; SCOPUS scopus
Abstract
Ceramide belongs to the group of sphingolipid metabolites that are produced in the brain and peripheral systems and act as intracellular second messengers. Although some physiological roles of ceramide have been reported in the brain, the role of ceramide in astrocytes has not been clearly demonstrated. In the present study, we investigated the antioxidant effects of the cell-permeable short-chain C2 ceramide in rat brain astrocytes. C2 ceramide inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. C2 ceramide increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1), and superoxide dismutase (SOD) that are under the control of Nrf2/ARE signaling pathways. Detailed mechanistic studies revealed that C2 ceramide increased the nuclear translocation and DNA binding of nuclear factor-E2-related factor 2 (Nrf2) and c-Jun to the antioxidant response element (ARE), and increased ARE-mediated transcriptional activity. Moreover, C2 ceramide increased the interaction between Nrf2 and c-Jun as shown by antibody co-immunoprecipitation assay. Further analysis of signaling pathways revealed that AMPK and MAP kinases are involved in HO-1 expression by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by C2 ceramide may be a potential therapeutic modality for neurodegenerative diseases that are accompanied by oxidative stress. © 2016 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.neuint.2016.02.004
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의학전문대학원 > 의학과 > Journal papers
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