| Regulation of oxidative stress in long-lived lipopolysaccharide-activated microglia. | |
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MedLine Citation:
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PMID: 22519637 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously reported that the optimal dose of lipopolysaccharide markedly extends the life span of mouse primary-cultured microglia by suppressing apoptotic and autophagic cell death pathways. This study was undertaken to assess how these cells protect themselves against reactive oxygen species generated by lipopolysaccharide treatment. We used microglia obtained from murine neonate brain, which are destined to die within a few days under ordinary culture conditions. The generation of reactive oxygen species reached maximum after 15 h of lipopolysaccharide treatment. The expression of inducible nitric oxide synthase protein was significantly increased by day 1 of lipopolysaccharide treatment and was followed by the production of nitric oxide. The expression of either copper/zinc or manganese superoxide dismutase protein was also increased by 16 h and day 1 of lipopolysaccharide treatment. Lipopolysaccharide did not affect the expressions of copper/zinc- and manganese-superoxide dismutase proteins nor extend the life span of microglia possessing mutated Toll-like receptor 4. Our findings suggest that superoxide dismutases function as a potent barrier to overcome reactive oxygen species generated in primary-cultured microglia under lipopolysaccharide treatment and that Toll-like receptor 4 may be deeply involved in inducing these proteins. The microglia may be able to protect themselves against oxidative stress, allowing them to live for more than 1 month. Because long-lived microglia may play critical roles in the exacerbation of neurodegeneration, bringing activated microglia back to their resting stage could be a new and promising strategy to inhibit the deterioration underlying neurodegenerative disorders. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd. |
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Authors:
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Yoko S Kaneko; Akira Ota; Akira Nakashima; Keiji Mori; Ikuko Nagatsu; Toshiharu Nagatsu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-23 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: - ISSN: 1440-1681 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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Department of Physiology, Fujita Health University School of Medicine, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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