Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades
Chromogranin A (CgA), a neuroactive glycoprotein, is associated with microglial activation cascades implicated in neurodegeneration. Here we show that CgA-dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), s...
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| Veröffentlicht in: | FEBS letters 2009-11, Vol.583 (21), p.3461-3466 |
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| creator | Hooper, Claudie Fry, Victoria A.H. Sevastou, Ioanna G. Pocock, Jennifer M. |
| description | Chromogranin A (CgA), a neuroactive glycoprotein, is associated with microglial activation cascades implicated in neurodegeneration. Here we show that CgA-dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), since SR class-A (SR-A) ligands blocked iNOS expression, mitochondrial depolarisation, apoptosis and glutamate release. Furthermore, block of SR-A ameliorated CgA-induced microglial neurotoxicity. In contrast, block of CD36, or the receptor for advanced glycation end products (RAGE) did not prevent CgA-induced microglial activation and neurotoxicity. Thus, manipulation of specific scavenger receptor-coupled signalling pathways may provide avenues for therapeutic intervention in neurodegenerative diseases implicating microglial activation with chromogranin peptides. |
| doi_str_mv | 10.1016/j.febslet.2009.09.049 |
| format | Article |
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Here we show that CgA-dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), since SR class-A (SR-A) ligands blocked iNOS expression, mitochondrial depolarisation, apoptosis and glutamate release. Furthermore, block of SR-A ameliorated CgA-induced microglial neurotoxicity. In contrast, block of CD36, or the receptor for advanced glycation end products (RAGE) did not prevent CgA-induced microglial activation and neurotoxicity. 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Here we show that CgA-dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), since SR class-A (SR-A) ligands blocked iNOS expression, mitochondrial depolarisation, apoptosis and glutamate release. Furthermore, block of SR-A ameliorated CgA-induced microglial neurotoxicity. In contrast, block of CD36, or the receptor for advanced glycation end products (RAGE) did not prevent CgA-induced microglial activation and neurotoxicity. Thus, manipulation of specific scavenger receptor-coupled signalling pathways may provide avenues for therapeutic intervention in neurodegenerative diseases implicating microglial activation with chromogranin peptides.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Amino Acid Sequence</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cell stress</subject><subject>Chromogranin A - chemistry</subject><subject>Chromogranin A - toxicity</subject><subject>Microglia</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Neurodegeneration</subject><subject>Neurotoxins - chemistry</subject><subject>Neurotoxins - toxicity</subject><subject>Plaque, Amyloid - drug effects</subject><subject>Plaque, Amyloid - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Scavenger - metabolism</subject><subject>Scavenger receptor</subject><subject>Scavenger Receptors, Class A - metabolism</subject><subject>Signal Transduction - drug effects</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9r3DAQxUVoSTabfIQUnXrzVrJsr3QqadgkhUAPaa8VI2m80WJLW8nOn28fm13osYWBQfDmaeb3CLnibMUZb77sVi2a3OGwKhlTq7kqdUIWXK5FIapGfiALxnhV1Gslzsh5zjs2vSVXp-SMK8mYlGJBfj9aeMawxUQTWtwPMVEbw5BiR2NL7VOKfdwmCD7Q68IHN1p0tPc2xW3noaN5SJgzheBowDHFIb56Sy1kCw7zBfnYQpfx8tiX5Nft5ufNffHw4-77zfVDYeuyqQoj1gakM03rnLJSGi4AgTsQrBFKgTTGNBbASVcyMKAayXkt0NZc2fmQJfl88N2n-GfEPOjeZ4tdBwHjmHXJS17JspqE9UE4HZBzwlbvk-8hvWnO9AxW7_QRrJ7B6rkqNc19On4wmh7d36kjyUlwfxC8-A7f_s9V326-lY9zSnNITDG2rsW849eDFU7Enj0mna3HMIH3U0aDdtH_Y9t3bW-kcQ</recordid><startdate>20091103</startdate><enddate>20091103</enddate><creator>Hooper, Claudie</creator><creator>Fry, Victoria A.H.</creator><creator>Sevastou, Ioanna G.</creator><creator>Pocock, Jennifer M.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>7TK</scope><scope>C1K</scope><scope>SOI</scope></search><sort><creationdate>20091103</creationdate><title>Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades</title><author>Hooper, Claudie ; Fry, Victoria A.H. ; Sevastou, Ioanna G. ; Pocock, Jennifer M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5264-b37ba8db6fdd9c88b13aea1da306399a8bbb6caad8d20aba9681153ec519c0883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Amino Acid Sequence</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cell stress</topic><topic>Chromogranin A - chemistry</topic><topic>Chromogranin A - toxicity</topic><topic>Microglia</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Neurodegeneration</topic><topic>Neurotoxins - chemistry</topic><topic>Neurotoxins - toxicity</topic><topic>Plaque, Amyloid - drug effects</topic><topic>Plaque, Amyloid - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Scavenger - metabolism</topic><topic>Scavenger receptor</topic><topic>Scavenger Receptors, Class A - metabolism</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hooper, Claudie</creatorcontrib><creatorcontrib>Fry, Victoria A.H.</creatorcontrib><creatorcontrib>Sevastou, Ioanna G.</creatorcontrib><creatorcontrib>Pocock, Jennifer M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hooper, Claudie</au><au>Fry, Victoria A.H.</au><au>Sevastou, Ioanna G.</au><au>Pocock, Jennifer M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2009-11-03</date><risdate>2009</risdate><volume>583</volume><issue>21</issue><spage>3461</spage><epage>3466</epage><pages>3461-3466</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Chromogranin A (CgA), a neuroactive glycoprotein, is associated with microglial activation cascades implicated in neurodegeneration. 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| subjects | Alzheimer Disease - drug therapy Alzheimer Disease - pathology Alzheimer's disease Amino Acid Sequence Amyloid beta-Peptides - metabolism Animals Cell Line Cell stress Chromogranin A - chemistry Chromogranin A - toxicity Microglia Microglia - drug effects Microglia - metabolism Molecular Sequence Data Neurodegeneration Neurotoxins - chemistry Neurotoxins - toxicity Plaque, Amyloid - drug effects Plaque, Amyloid - metabolism Rats Rats, Wistar Receptors, Scavenger - metabolism Scavenger receptor Scavenger Receptors, Class A - metabolism Signal Transduction - drug effects |
| title | Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades |
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