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Lonchocarpine increases Nrf2/ARE-mediated antioxidant enzyme expression by modulating AMPK and MAPK signaling in brain astrocytes

Title
Lonchocarpine increases Nrf2/ARE-mediated antioxidant enzyme expression by modulating AMPK and MAPK signaling in brain astrocytes
Authors
Jeong Y.-H.Park J.-S.Kim D.-H.Kim H.-S.
Ewha Authors
김희선
SCOPUS Author ID
김희선scopus
Issue Date
2016
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
vol. 24, no. 6, pp. 581 - 588
Keywords
AMPKAntioxidant enzymesAstrocytesLonchocarpineMAPKNrf2/ARE signaling
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Lonchocarpine is a phenylpropanoid compound isolated from Abrus precatorius that has anti-bacterial,anti-inflammatory,antiproliferative,and antiepileptic activities. In the present study,we investigated the antioxidant effects of lonchocarpine in brain glial cells and analyzed its molecular mechanisms. We found that lonchocarpine suppressed reactive oxygen species (ROS) production and cell death in hydrogen peroxide-treated primary astrocytes. In addition,lonchocarpine increased the expression of antioxidant enzymes,such as heme oxygenase-1 (HO-1),NAD(P)H:quinone oxidoreductase 1 (NQO1),and manganese superoxide dismutase (MnSOD),which are all under the control of Nrf2/antioxidant response element (ARE) signaling. Further,mechanistic studies showed that lonchocarpine increases the nuclear translocation and DNA binding of Nrf2 to ARE as well as ARE-mediated transcriptional activities. Moreover,lonchocarpine increased the phosphorylation of AMP-activated protein kinase (AMPK) and three types of mitogen-activated protein kinases (MAPKs). By treating astrocytes with each signaling pathway-specific inhibitor,AMPK,c-jun N-terminal protein kinase (JNK),and p38 MAPK were identified to be involved in lonchocarpine-induced HO-1 expression and ARE-mediated transcriptional activities. Therefore,lonchocarpine may be a potential therapeutic agent for neurodegenerative diseases that are associated with oxidative stress. © 2016 The Korean Society of Applied Pharmacology.
DOI
10.4062/biomolther.2016.141
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의학전문대학원 > 의학과 > Journal papers
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