Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42
Melatonin shows significant protective effects in Alzheimer's disease (AD) models in vitro and in vivo; these effects are related to its function as an antioxidant. The source of reactive oxygen species (ROS) generation in the AD brain is primarily the amyloid-beta (Abeta)- activated microglial...
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| Veröffentlicht in: | Journal of pineal research 2008-09, Vol.45 (2), p.157-165 |
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| creator | Zhou, Juefei Zhang, Shen Zhao, Xingyu Wei, Taotao |
| description | Melatonin shows significant protective effects in Alzheimer's disease (AD) models in vitro and in vivo; these effects are related to its function as an antioxidant. The source of reactive oxygen species (ROS) generation in the AD brain is primarily the amyloid-beta (Abeta)- activated microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, the effects of melatonin on the activation of NADPH oxidase remain unclear. In the present study, the cultures of microglia were incubated in the presence of fibrillar Abeta(1-42), which induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived ROS. Pretreatment of microglia with melatonin dose-dependently prevents the activation of NADPH oxidase and decreases the production of ROS. Melatonin inhibits the phosphorylation of the p47(phox) subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47(phox) and p67(phox) subunit to the membrane, down-regulates the binding of p47(phox) to gp91(phox), and impairs the assembly of NADPH oxidase. Our data offer new insights into the mechanism of inhibiting ROS generation by melatonin in Abeta-activated microglia. Inhibition of ROS production indirectly might be the underlying mechanism for the neuroprotection by melatonin in the AD brain. |
| doi_str_mv | 10.1111/j.1600-079X.2008.00570.x |
| format | Article |
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The source of reactive oxygen species (ROS) generation in the AD brain is primarily the amyloid-beta (Abeta)- activated microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, the effects of melatonin on the activation of NADPH oxidase remain unclear. In the present study, the cultures of microglia were incubated in the presence of fibrillar Abeta(1-42), which induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived ROS. Pretreatment of microglia with melatonin dose-dependently prevents the activation of NADPH oxidase and decreases the production of ROS. Melatonin inhibits the phosphorylation of the p47(phox) subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47(phox) and p67(phox) subunit to the membrane, down-regulates the binding of p47(phox) to gp91(phox), and impairs the assembly of NADPH oxidase. Our data offer new insights into the mechanism of inhibiting ROS generation by melatonin in Abeta-activated microglia. Inhibition of ROS production indirectly might be the underlying mechanism for the neuroprotection by melatonin in the AD brain.</description><identifier>EISSN: 1600-079X</identifier><identifier>DOI: 10.1111/j.1600-079X.2008.00570.x</identifier><identifier>PMID: 18298462</identifier><language>eng</language><publisher>England</publisher><subject>Amyloid beta-Peptides - pharmacology ; Animals ; Animals, Newborn ; Antioxidants - pharmacology ; Blotting, Western ; Cell Membrane - metabolism ; Cells, Cultured ; Electron Spin Resonance Spectroscopy ; Immunoprecipitation ; Melatonin - pharmacology ; Microglia - cytology ; Microglia - drug effects ; Microglia - metabolism ; NADPH Oxidases - metabolism ; Phosphoproteins - metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species - metabolism ; Superoxides - metabolism</subject><ispartof>Journal of pineal research, 2008-09, Vol.45 (2), p.157-165</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1092-e80cab40b7e24f35197df664a4dd223802df330a24a0d245abf99fec483e55ec3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18298462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Juefei</creatorcontrib><creatorcontrib>Zhang, Shen</creatorcontrib><creatorcontrib>Zhao, Xingyu</creatorcontrib><creatorcontrib>Wei, Taotao</creatorcontrib><title>Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42</title><title>Journal of pineal research</title><addtitle>J Pineal Res</addtitle><description>Melatonin shows significant protective effects in Alzheimer's disease (AD) models in vitro and in vivo; these effects are related to its function as an antioxidant. The source of reactive oxygen species (ROS) generation in the AD brain is primarily the amyloid-beta (Abeta)- activated microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, the effects of melatonin on the activation of NADPH oxidase remain unclear. In the present study, the cultures of microglia were incubated in the presence of fibrillar Abeta(1-42), which induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived ROS. Pretreatment of microglia with melatonin dose-dependently prevents the activation of NADPH oxidase and decreases the production of ROS. Melatonin inhibits the phosphorylation of the p47(phox) subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47(phox) and p67(phox) subunit to the membrane, down-regulates the binding of p47(phox) to gp91(phox), and impairs the assembly of NADPH oxidase. Our data offer new insights into the mechanism of inhibiting ROS generation by melatonin in Abeta-activated microglia. Inhibition of ROS production indirectly might be the underlying mechanism for the neuroprotection by melatonin in the AD brain.</description><subject>Amyloid beta-Peptides - pharmacology</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antioxidants - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Membrane - metabolism</subject><subject>Cells, Cultured</subject><subject>Electron Spin Resonance Spectroscopy</subject><subject>Immunoprecipitation</subject><subject>Melatonin - pharmacology</subject><subject>Microglia - cytology</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>NADPH Oxidases - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Superoxides - metabolism</subject><issn>1600-079X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFtLw0AQhRdBbK3-Bdkn3xIne0k2j6VeKtTLg4JvYbM7kS1JNmYTaPHPm2J1XuYw5-NwGEJoAnEyzc02TlKACLL8I2YAKgaQGcS7EzL_N2bkPIQtTK5S6RmZJYrlSqRsTr6fsNaDb11LXdNp1wf6vLx9XVO_c1YHpDoEbMp6T3VrqUXT43QNNIwd9gdmIlrnW9r13o5mOMgpq3Gm95-10xR3nQ9o6eCpbva1dzYqcdBJJNgFOa10HfDyuBfk_f7ubbWONi8Pj6vlJjIJ5CxCBUaXAsoMmai4TPLMVmkqtLCWMa6A2Ypz0ExosExIXVZ5XqERiqOUaPiCXP_mTh2_RgxD0bhgsK51i34MRZpLxaWECbw6gmPZoC263jW63xd_7-I_K9luYg</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Zhou, Juefei</creator><creator>Zhang, Shen</creator><creator>Zhao, Xingyu</creator><creator>Wei, Taotao</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200809</creationdate><title>Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42</title><author>Zhou, Juefei ; Zhang, Shen ; Zhao, Xingyu ; Wei, Taotao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1092-e80cab40b7e24f35197df664a4dd223802df330a24a0d245abf99fec483e55ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Amyloid beta-Peptides - pharmacology</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antioxidants - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Membrane - metabolism</topic><topic>Cells, Cultured</topic><topic>Electron Spin Resonance Spectroscopy</topic><topic>Immunoprecipitation</topic><topic>Melatonin - pharmacology</topic><topic>Microglia - cytology</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>NADPH Oxidases - metabolism</topic><topic>Phosphoproteins - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Superoxides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Juefei</creatorcontrib><creatorcontrib>Zhang, Shen</creatorcontrib><creatorcontrib>Zhao, Xingyu</creatorcontrib><creatorcontrib>Wei, Taotao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pineal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Juefei</au><au>Zhang, Shen</au><au>Zhao, Xingyu</au><au>Wei, Taotao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42</atitle><jtitle>Journal of pineal research</jtitle><addtitle>J Pineal Res</addtitle><date>2008-09</date><risdate>2008</risdate><volume>45</volume><issue>2</issue><spage>157</spage><epage>165</epage><pages>157-165</pages><eissn>1600-079X</eissn><abstract>Melatonin shows significant protective effects in Alzheimer's disease (AD) models in vitro and in vivo; these effects are related to its function as an antioxidant. The source of reactive oxygen species (ROS) generation in the AD brain is primarily the amyloid-beta (Abeta)- activated microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, the effects of melatonin on the activation of NADPH oxidase remain unclear. In the present study, the cultures of microglia were incubated in the presence of fibrillar Abeta(1-42), which induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived ROS. Pretreatment of microglia with melatonin dose-dependently prevents the activation of NADPH oxidase and decreases the production of ROS. Melatonin inhibits the phosphorylation of the p47(phox) subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47(phox) and p67(phox) subunit to the membrane, down-regulates the binding of p47(phox) to gp91(phox), and impairs the assembly of NADPH oxidase. Our data offer new insights into the mechanism of inhibiting ROS generation by melatonin in Abeta-activated microglia. Inhibition of ROS production indirectly might be the underlying mechanism for the neuroprotection by melatonin in the AD brain.</abstract><cop>England</cop><pmid>18298462</pmid><doi>10.1111/j.1600-079X.2008.00570.x</doi><tpages>9</tpages></addata></record> |
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| subjects | Amyloid beta-Peptides - pharmacology Animals Animals, Newborn Antioxidants - pharmacology Blotting, Western Cell Membrane - metabolism Cells, Cultured Electron Spin Resonance Spectroscopy Immunoprecipitation Melatonin - pharmacology Microglia - cytology Microglia - drug effects Microglia - metabolism NADPH Oxidases - metabolism Phosphoproteins - metabolism Rats Rats, Sprague-Dawley Reactive Oxygen Species - metabolism Superoxides - metabolism |
| title | Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42 |
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