Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors
An in vitro ischemia model (oxygen, glucose, and serum deprivation) is used to investigate the possible cellular and molecular mechanisms responsible for cerebral ischemia. We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing...
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| Veröffentlicht in: | Experimental neurology 2006-09, Vol.201 (1), p.225-233 |
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| creator | Lin, Chi-Hsin Cheng, Fu-Chou Lu, Yen-Zhen Chu, Lan-Feng Wang, Chen-Hsuan Hsueh, Chi-Mei |
| description | An in vitro ischemia model (oxygen, glucose, and serum deprivation) is used to investigate the possible cellular and molecular mechanisms responsible for cerebral ischemia. We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing GDNF and TGF-β1. In the present study, we investigate whether products of ischemic astrocytes can also protect ischemic microglia, astrocytes, and neurons in a similar manner. Supernatants from ischemic astrocytes were collected after various periods of ischemia and incubated with microglia, astrocytes, or neurons individually, under in vitro ischemic conditions. The components responsible for the protective effects of astrocyte-derived supernatants were then identified by Western blot, ELISA, trypan blue dye exclusion, and immunoblocking assays. Results showed that under conditions of in vitro ischemia the number of surviving microglia, astrocytes, and neurons was significantly increased by the incorporation of the astrocyte-derived supernatants. Astrocyte supernatant-mediated protection of ischemic microglia was dependent on TGF-β1 and NT-3, ischemic astrocytes were protected by GDNF, and ischemic neurons were protected by NT-3. In addition, protein expression of TGF-β1 and NT-3 receptors in microglia, GDNF receptors in astrocytes, and NT-3 receptors in neurons was increased by in vitro ischemia. These results suggest that astrocyte-derived protection of ischemic brain cells is dependent not only on factors released from the ischemic astrocytes, but also on the type of receptor present on the responding cells. Therapeutic potential of TGF-β1, GDNF, and NT-3 in the control of cerebral ischemia is further suggested. |
| doi_str_mv | 10.1016/j.expneurol.2006.04.014 |
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We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing GDNF and TGF-β1. In the present study, we investigate whether products of ischemic astrocytes can also protect ischemic microglia, astrocytes, and neurons in a similar manner. Supernatants from ischemic astrocytes were collected after various periods of ischemia and incubated with microglia, astrocytes, or neurons individually, under in vitro ischemic conditions. The components responsible for the protective effects of astrocyte-derived supernatants were then identified by Western blot, ELISA, trypan blue dye exclusion, and immunoblocking assays. Results showed that under conditions of in vitro ischemia the number of surviving microglia, astrocytes, and neurons was significantly increased by the incorporation of the astrocyte-derived supernatants. Astrocyte supernatant-mediated protection of ischemic microglia was dependent on TGF-β1 and NT-3, ischemic astrocytes were protected by GDNF, and ischemic neurons were protected by NT-3. In addition, protein expression of TGF-β1 and NT-3 receptors in microglia, GDNF receptors in astrocytes, and NT-3 receptors in neurons was increased by in vitro ischemia. These results suggest that astrocyte-derived protection of ischemic brain cells is dependent not only on factors released from the ischemic astrocytes, but also on the type of receptor present on the responding cells. Therapeutic potential of TGF-β1, GDNF, and NT-3 in the control of cerebral ischemia is further suggested.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2006.04.014</identifier><identifier>PMID: 16765947</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Astrocytes ; Astrocytes - cytology ; Astrocytes - drug effects ; Astrocytes - secretion ; Biological and medical sciences ; Blotting, Western ; Brain - cytology ; Brain - drug effects ; Brain - metabolism ; Cell Hypoxia ; Cells, Cultured ; Culture Media, Conditioned - metabolism ; Culture Media, Conditioned - pharmacology ; Development. Senescence. Regeneration. Transplantation ; Enzyme-Linked Immunosorbent Assay ; Fundamental and applied biological sciences. Psychology ; GDNF ; Glial Cell Line-Derived Neurotrophic Factor - pharmacology ; Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism ; Growth Substances - pharmacology ; In vitro ischemia ; Medical sciences ; Microglia ; Microglia - cytology ; Microglia - drug effects ; Microglia - metabolism ; Neurology ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Neurotrophin 3 - pharmacology ; NT-3 ; Rats ; Rats, Sprague-Dawley ; Receptor, trkC - metabolism ; Receptors, Growth Factor - metabolism ; Receptors, Transforming Growth Factor beta - metabolism ; TGF-β1 ; Time Factors ; Transforming Growth Factor beta - pharmacology ; Transforming Growth Factor beta1 ; Vascular diseases and vascular malformations of the nervous system ; Vertebrates: nervous system and sense organs</subject><ispartof>Experimental neurology, 2006-09, Vol.201 (1), p.225-233</ispartof><rights>2006</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-fbb469596bf09a196ff6fc9a337795523329f08d2a51f2e025c3a4269a2517c93</citedby><cites>FETCH-LOGICAL-c399t-fbb469596bf09a196ff6fc9a337795523329f08d2a51f2e025c3a4269a2517c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2006.04.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18074613$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16765947$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Chi-Hsin</creatorcontrib><creatorcontrib>Cheng, Fu-Chou</creatorcontrib><creatorcontrib>Lu, Yen-Zhen</creatorcontrib><creatorcontrib>Chu, Lan-Feng</creatorcontrib><creatorcontrib>Wang, Chen-Hsuan</creatorcontrib><creatorcontrib>Hsueh, Chi-Mei</creatorcontrib><title>Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>An in vitro ischemia model (oxygen, glucose, and serum deprivation) is used to investigate the possible cellular and molecular mechanisms responsible for cerebral ischemia. We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing GDNF and TGF-β1. In the present study, we investigate whether products of ischemic astrocytes can also protect ischemic microglia, astrocytes, and neurons in a similar manner. Supernatants from ischemic astrocytes were collected after various periods of ischemia and incubated with microglia, astrocytes, or neurons individually, under in vitro ischemic conditions. The components responsible for the protective effects of astrocyte-derived supernatants were then identified by Western blot, ELISA, trypan blue dye exclusion, and immunoblocking assays. Results showed that under conditions of in vitro ischemia the number of surviving microglia, astrocytes, and neurons was significantly increased by the incorporation of the astrocyte-derived supernatants. Astrocyte supernatant-mediated protection of ischemic microglia was dependent on TGF-β1 and NT-3, ischemic astrocytes were protected by GDNF, and ischemic neurons were protected by NT-3. In addition, protein expression of TGF-β1 and NT-3 receptors in microglia, GDNF receptors in astrocytes, and NT-3 receptors in neurons was increased by in vitro ischemia. These results suggest that astrocyte-derived protection of ischemic brain cells is dependent not only on factors released from the ischemic astrocytes, but also on the type of receptor present on the responding cells. Therapeutic potential of TGF-β1, GDNF, and NT-3 in the control of cerebral ischemia is further suggested.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Astrocytes</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - secretion</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Brain - cytology</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cell Hypoxia</subject><subject>Cells, Cultured</subject><subject>Culture Media, Conditioned - metabolism</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Development. Senescence. Regeneration. Transplantation</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GDNF</subject><subject>Glial Cell Line-Derived Neurotrophic Factor - pharmacology</subject><subject>Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism</subject><subject>Growth Substances - pharmacology</subject><subject>In vitro ischemia</subject><subject>Medical sciences</subject><subject>Microglia</subject><subject>Microglia - cytology</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurotrophin 3 - pharmacology</subject><subject>NT-3</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, trkC - metabolism</subject><subject>Receptors, Growth Factor - metabolism</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>TGF-β1</subject><subject>Time Factors</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Transforming Growth Factor beta1</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtv1DAURi0EotPCXwBvYJdw_YgTL6uqPKRKsIC15TjXHY8ycbA9Lf33eDQjumR1pU_nvg4h7xm0DJj6tGvxz7rgIcW55QCqBdkCky_IhoGGhksBL8kGatTIYVAX5DLnHQBoyfvX5IKpXnVa9hty_yPFgq6EuNDoachui_vg6JhsWKjDec41pBOuuEy4FFo5m0uK7qlgM2EKDzjR-xQfy5Z660pMmdplomWLIdGEDtdj9oa88nbO-PZcr8ivz7c_b742d9-_fLu5vmuc0Lo0fhyl0p1WowdtmVbeK--0FaLvdddxIbj2MEzcdsxzBN45YSVX2vKO9U6LK_LxNHdN8fcBczH7-lN9wy4YD9moYZCgxBHsT6BLMeeE3qwp7G16MgzM0bHZmX-OzdGxAWmq0Nr57rziMO5xeu47S63AhzNgs7OzT3ZxIT9zA_RSMVG56xOHVchDwGSyC7g4nEL1VswUw3-P-QtGj6BI</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Lin, Chi-Hsin</creator><creator>Cheng, Fu-Chou</creator><creator>Lu, Yen-Zhen</creator><creator>Chu, Lan-Feng</creator><creator>Wang, Chen-Hsuan</creator><creator>Hsueh, Chi-Mei</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20060901</creationdate><title>Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors</title><author>Lin, Chi-Hsin ; Cheng, Fu-Chou ; Lu, Yen-Zhen ; Chu, Lan-Feng ; Wang, Chen-Hsuan ; Hsueh, Chi-Mei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-fbb469596bf09a196ff6fc9a337795523329f08d2a51f2e025c3a4269a2517c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Astrocytes</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - secretion</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Brain - cytology</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cell Hypoxia</topic><topic>Cells, Cultured</topic><topic>Culture Media, Conditioned - metabolism</topic><topic>Culture Media, Conditioned - pharmacology</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>GDNF</topic><topic>Glial Cell Line-Derived Neurotrophic Factor - pharmacology</topic><topic>Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism</topic><topic>Growth Substances - pharmacology</topic><topic>In vitro ischemia</topic><topic>Medical sciences</topic><topic>Microglia</topic><topic>Microglia - cytology</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurotrophin 3 - pharmacology</topic><topic>NT-3</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, trkC - metabolism</topic><topic>Receptors, Growth Factor - metabolism</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>TGF-β1</topic><topic>Time Factors</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>Transforming Growth Factor beta1</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Chi-Hsin</creatorcontrib><creatorcontrib>Cheng, Fu-Chou</creatorcontrib><creatorcontrib>Lu, Yen-Zhen</creatorcontrib><creatorcontrib>Chu, Lan-Feng</creatorcontrib><creatorcontrib>Wang, Chen-Hsuan</creatorcontrib><creatorcontrib>Hsueh, Chi-Mei</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Chi-Hsin</au><au>Cheng, Fu-Chou</au><au>Lu, Yen-Zhen</au><au>Chu, Lan-Feng</au><au>Wang, Chen-Hsuan</au><au>Hsueh, Chi-Mei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2006-09-01</date><risdate>2006</risdate><volume>201</volume><issue>1</issue><spage>225</spage><epage>233</epage><pages>225-233</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>An in vitro ischemia model (oxygen, glucose, and serum deprivation) is used to investigate the possible cellular and molecular mechanisms responsible for cerebral ischemia. We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing GDNF and TGF-β1. In the present study, we investigate whether products of ischemic astrocytes can also protect ischemic microglia, astrocytes, and neurons in a similar manner. Supernatants from ischemic astrocytes were collected after various periods of ischemia and incubated with microglia, astrocytes, or neurons individually, under in vitro ischemic conditions. The components responsible for the protective effects of astrocyte-derived supernatants were then identified by Western blot, ELISA, trypan blue dye exclusion, and immunoblocking assays. Results showed that under conditions of in vitro ischemia the number of surviving microglia, astrocytes, and neurons was significantly increased by the incorporation of the astrocyte-derived supernatants. Astrocyte supernatant-mediated protection of ischemic microglia was dependent on TGF-β1 and NT-3, ischemic astrocytes were protected by GDNF, and ischemic neurons were protected by NT-3. In addition, protein expression of TGF-β1 and NT-3 receptors in microglia, GDNF receptors in astrocytes, and NT-3 receptors in neurons was increased by in vitro ischemia. These results suggest that astrocyte-derived protection of ischemic brain cells is dependent not only on factors released from the ischemic astrocytes, but also on the type of receptor present on the responding cells. Therapeutic potential of TGF-β1, GDNF, and NT-3 in the control of cerebral ischemia is further suggested.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>16765947</pmid><doi>10.1016/j.expneurol.2006.04.014</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Animals, Newborn Astrocytes Astrocytes - cytology Astrocytes - drug effects Astrocytes - secretion Biological and medical sciences Blotting, Western Brain - cytology Brain - drug effects Brain - metabolism Cell Hypoxia Cells, Cultured Culture Media, Conditioned - metabolism Culture Media, Conditioned - pharmacology Development. Senescence. Regeneration. Transplantation Enzyme-Linked Immunosorbent Assay Fundamental and applied biological sciences. Psychology GDNF Glial Cell Line-Derived Neurotrophic Factor - pharmacology Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism Growth Substances - pharmacology In vitro ischemia Medical sciences Microglia Microglia - cytology Microglia - drug effects Microglia - metabolism Neurology Neurons Neurons - cytology Neurons - drug effects Neurons - metabolism Neurotrophin 3 - pharmacology NT-3 Rats Rats, Sprague-Dawley Receptor, trkC - metabolism Receptors, Growth Factor - metabolism Receptors, Transforming Growth Factor beta - metabolism TGF-β1 Time Factors Transforming Growth Factor beta - pharmacology Transforming Growth Factor beta1 Vascular diseases and vascular malformations of the nervous system Vertebrates: nervous system and sense organs |
| title | Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors |
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