| Effects of Obovatol on GSH Depleted Glia-Mediated Neurotoxicity and Oxidative Damage. | |
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MedLine Citation:
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PMID: 21796424 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Earlier studies indicate that obovatol (OBO), isolated from a medicinal herb Magnolia obovata, has anti-inflammatory and anti-oxidative properties. Depletion of glutathione (GSH) in glial cells with the γ-glutamylcysteine synthase inhibitor D,L-buthionine-S,R-sulfoximine (BSO) is known to produce oxidative stress which, in turn, induces these cells to secrete inflammatory cytokines and other neurotoxic substances. In the present study, we investigated the ability of OBO to protect SH-SY5Y neuroblastoma cells from this effect. Human microglia, astrocytes and their surrogate THP-1 and U373 cell lines were activated by treatment with BSO. Such treatment depleted their intracellular GSH and increased levels of damage to DNA, lipids and proteins (8-OHdG, lipid peroxide, protein carbonyls and 3-nitrotyrosine), and activated the inflammatory pathways P38 MAP kinase and NFκB. These are accompanied by release of proinflammatory factors such as TNFα, IL-6 and nitric oxide. Their conditioned media were toxic to SH-SY5Y cells. All these effects were attenuated by pre-treatment with OBO. Prior treatment of SH-SY5Y cells with OBO also attenuated THP-1 or U373 conditioned media neurotoxicity and also reduced oxidative damage produced by treatment with hydrogen peroxide or BSO. Prior treatment with OBO potentiated survival of SH-SY5Y cells exposed to conditioned medium from BSO-treated THP-1, U373 cells, microglia and astrocytes. The data indicate that OBO could be anti-inflammatory, anti-oxidative and neuroprotective, and be an effective agent for inhibiting pathogenesis in neurological diseases such as Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis in which glial-mediated neuroinflammation and oxidative stress are thought to contribute to disease progression. |
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Authors:
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Moonhee Lee; Byoung-Mok Kwon; Kyoungho Suk; Edith McGeer; Patrick L McGeer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-28 |
Journal Detail:
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Title: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology Volume: - ISSN: 1557-1904 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada, V6T 1Z3. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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