Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells
Abstract Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transie...
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| Veröffentlicht in: | Brain research 2011-02, Vol.1375, p.28-40 |
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| creator | Sánchez-Muñoz, Isabel Sánchez-Franco, Franco Vallejo, Mario Fernández, Antonio Palacios, Nuria Fernández, Miriam Sánchez-Grande, María Cacicedo, Lucinda |
| description | Abstract Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transiently transfected with different constructs of the SS promoter fused to the luciferase and CAT reporter genes. We demonstrated that BDNF triggered the transcription of the SS gene through the CRE sequence located in the SS promoter. BDNF and SS are genes regulated by K+ -induced neuronal activity. Using BDNF blocking antibodies, we investigated whether K+ -induced BDNF was required for K+ -dependent SS mRNA induction. We found that K+ -induced SS mRNA was partially prevented when BDNF was blocked. This finding indicated that BDNF mediated the induction of SS mRNA by K+ depolarization. To identify the mechanisms by which BDNF activates SS gene transcription we first elucidated the signaling pathways activated by BDNF in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89 and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We next elucidated the mechanism by which BDNF induces SS mRNA. We observed that H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK and PI3K pathways. |
| doi_str_mv | 10.1016/j.brainres.2010.12.031 |
| format | Article |
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To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transiently transfected with different constructs of the SS promoter fused to the luciferase and CAT reporter genes. We demonstrated that BDNF triggered the transcription of the SS gene through the CRE sequence located in the SS promoter. BDNF and SS are genes regulated by K+ -induced neuronal activity. Using BDNF blocking antibodies, we investigated whether K+ -induced BDNF was required for K+ -dependent SS mRNA induction. We found that K+ -induced SS mRNA was partially prevented when BDNF was blocked. This finding indicated that BDNF mediated the induction of SS mRNA by K+ depolarization. To identify the mechanisms by which BDNF activates SS gene transcription we first elucidated the signaling pathways activated by BDNF in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89 and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We next elucidated the mechanism by which BDNF induces SS mRNA. We observed that H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK and PI3K pathways.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2010.12.031</identifier><identifier>PMID: 21184749</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; antibodies ; BDNF ; Biological and medical sciences ; Blotting, Western ; brain ; Brain-Derived Neurotrophic Factor - antagonists & inhibitors ; Brain-Derived Neurotrophic Factor - pharmacology ; Cell physiology ; Cells, Cultured ; Cerebral Cortex - drug effects ; Cerebral Cortex - metabolism ; CREB-CRE ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Electric Stimulation ; Enzyme Activation - drug effects ; Enzyme Inhibitors - pharmacology ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Immunoglobulin G - isolation & purification ; luciferase ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Molecular and cellular biology ; Neurology ; neurons ; phosphatidylinositol 3-kinase ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Potassium - pharmacology ; Pregnancy ; promoter regions ; Rats ; Rats, Sprague-Dawley ; Regulatory Elements, Transcriptional ; reporter genes ; Responses to growth factors, tumor promotors, other factors ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; signal transduction ; Signal Transduction - drug effects ; Signaling pathway ; somatostatin ; Somatostatin - biosynthesis ; Somatostatin - genetics ; transcription (genetics) ; Transcription, Genetic - drug effects ; Transfection</subject><ispartof>Brain research, 2011-02, Vol.1375, p.28-40</ispartof><rights>Elsevier B.V.</rights><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c574t-6f6b7091e3546e5774aa9737fb4358f7c9a4fe391030e8f238692e0376c8223e3</citedby><cites>FETCH-LOGICAL-c574t-6f6b7091e3546e5774aa9737fb4358f7c9a4fe391030e8f238692e0376c8223e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2010.12.031$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23912147$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21184749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sánchez-Muñoz, Isabel</creatorcontrib><creatorcontrib>Sánchez-Franco, Franco</creatorcontrib><creatorcontrib>Vallejo, Mario</creatorcontrib><creatorcontrib>Fernández, Antonio</creatorcontrib><creatorcontrib>Palacios, Nuria</creatorcontrib><creatorcontrib>Fernández, Miriam</creatorcontrib><creatorcontrib>Sánchez-Grande, María</creatorcontrib><creatorcontrib>Cacicedo, Lucinda</creatorcontrib><title>Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transiently transfected with different constructs of the SS promoter fused to the luciferase and CAT reporter genes. We demonstrated that BDNF triggered the transcription of the SS gene through the CRE sequence located in the SS promoter. BDNF and SS are genes regulated by K+ -induced neuronal activity. Using BDNF blocking antibodies, we investigated whether K+ -induced BDNF was required for K+ -dependent SS mRNA induction. We found that K+ -induced SS mRNA was partially prevented when BDNF was blocked. This finding indicated that BDNF mediated the induction of SS mRNA by K+ depolarization. To identify the mechanisms by which BDNF activates SS gene transcription we first elucidated the signaling pathways activated by BDNF in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89 and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We next elucidated the mechanism by which BDNF induces SS mRNA. We observed that H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK and PI3K pathways.</description><subject>Animals</subject><subject>antibodies</subject><subject>BDNF</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>brain</subject><subject>Brain-Derived Neurotrophic Factor - antagonists & inhibitors</subject><subject>Brain-Derived Neurotrophic Factor - pharmacology</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - metabolism</subject><subject>CREB-CRE</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Electric Stimulation</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Immunoglobulin G - isolation & purification</subject><subject>luciferase</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Molecular and cellular biology</subject><subject>Neurology</subject><subject>neurons</subject><subject>phosphatidylinositol 3-kinase</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Potassium - pharmacology</subject><subject>Pregnancy</subject><subject>promoter regions</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regulatory Elements, Transcriptional</subject><subject>reporter genes</subject><subject>Responses to growth factors, tumor promotors, other factors</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling pathway</subject><subject>somatostatin</subject><subject>Somatostatin - biosynthesis</subject><subject>Somatostatin - genetics</subject><subject>transcription (genetics)</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transfection</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAQxyMEokvhKxRfEKcsfiR2fEGgipdUCYlSiZvlOOPFSzZexk7FfnscdgsSl15seeY3D89_quqC0TWjTL7arnu0YUJIa04XI19TwR5UK9YpXkve0IfVilIq605rcVY9SWlbnkJo-rg644x1jWr0qsIvsJlHm0OcSPQkxZ3NMeVimMgGJiDwa1-KpMXfH8ifomQADLcwkAlmjBnj_ntwxFuXI5Li9pDtSNBm4gChx-gi5uCKzcE4pqfVI2_HBM9O93l18_7d18uP9dXnD58u317VrlVNrqWXvaKagWgbCa1SjbVaCeX7RrSdV07bxoPQjAoKneeik5oDFUq6jnMB4rx6ecy7x_hzhpTNLqSlAztBnJPpJBUdLcf9ZEvbVgulCimPpMOYEoI3eww7iwfDqFmEMVtzJ4xZhDGMmyJMCbw4lZj7HQx_w-6UKMCLE2BTGZVHO7mQ_nHlo5w1SwfPj5y30dgNFubmulRqi7pa8KYrxJsjAWW4twHQJBdgcjAEBJfNEMP93b7-L4Ubw7RI-AMOkLZxxqlIZ5hJJcBcL4u27BmjlEstv4nfFK_OWg</recordid><startdate>20110223</startdate><enddate>20110223</enddate><creator>Sánchez-Muñoz, Isabel</creator><creator>Sánchez-Franco, Franco</creator><creator>Vallejo, Mario</creator><creator>Fernández, Antonio</creator><creator>Palacios, Nuria</creator><creator>Fernández, Miriam</creator><creator>Sánchez-Grande, María</creator><creator>Cacicedo, Lucinda</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><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><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20110223</creationdate><title>Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells</title><author>Sánchez-Muñoz, Isabel ; Sánchez-Franco, Franco ; Vallejo, Mario ; Fernández, Antonio ; Palacios, Nuria ; Fernández, Miriam ; Sánchez-Grande, María ; Cacicedo, Lucinda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574t-6f6b7091e3546e5774aa9737fb4358f7c9a4fe391030e8f238692e0376c8223e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>antibodies</topic><topic>BDNF</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>brain</topic><topic>Brain-Derived Neurotrophic Factor - antagonists & inhibitors</topic><topic>Brain-Derived Neurotrophic Factor - pharmacology</topic><topic>Cell physiology</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - metabolism</topic><topic>CREB-CRE</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</topic><topic>Electric Stimulation</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Immunoglobulin G - isolation & purification</topic><topic>luciferase</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Molecular and cellular biology</topic><topic>Neurology</topic><topic>neurons</topic><topic>phosphatidylinositol 3-kinase</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Potassium - pharmacology</topic><topic>Pregnancy</topic><topic>promoter regions</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regulatory Elements, Transcriptional</topic><topic>reporter genes</topic><topic>Responses to growth factors, tumor promotors, other factors</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling pathway</topic><topic>somatostatin</topic><topic>Somatostatin - biosynthesis</topic><topic>Somatostatin - genetics</topic><topic>transcription (genetics)</topic><topic>Transcription, Genetic - drug effects</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sánchez-Muñoz, Isabel</creatorcontrib><creatorcontrib>Sánchez-Franco, Franco</creatorcontrib><creatorcontrib>Vallejo, Mario</creatorcontrib><creatorcontrib>Fernández, Antonio</creatorcontrib><creatorcontrib>Palacios, Nuria</creatorcontrib><creatorcontrib>Fernández, Miriam</creatorcontrib><creatorcontrib>Sánchez-Grande, María</creatorcontrib><creatorcontrib>Cacicedo, Lucinda</creatorcontrib><collection>AGRIS</collection><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><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sánchez-Muñoz, Isabel</au><au>Sánchez-Franco, Franco</au><au>Vallejo, Mario</au><au>Fernández, Antonio</au><au>Palacios, Nuria</au><au>Fernández, Miriam</au><au>Sánchez-Grande, María</au><au>Cacicedo, Lucinda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2011-02-23</date><risdate>2011</risdate><volume>1375</volume><spage>28</spage><epage>40</epage><pages>28-40</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Abstract Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by BDNF occurs at the transcriptional level and requires specific promoter sequences, cerebrocortical and PC12trkB neurons were transiently transfected with different constructs of the SS promoter fused to the luciferase and CAT reporter genes. We demonstrated that BDNF triggered the transcription of the SS gene through the CRE sequence located in the SS promoter. BDNF and SS are genes regulated by K+ -induced neuronal activity. Using BDNF blocking antibodies, we investigated whether K+ -induced BDNF was required for K+ -dependent SS mRNA induction. We found that K+ -induced SS mRNA was partially prevented when BDNF was blocked. This finding indicated that BDNF mediated the induction of SS mRNA by K+ depolarization. To identify the mechanisms by which BDNF activates SS gene transcription we first elucidated the signaling pathways activated by BDNF in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89 and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We next elucidated the mechanism by which BDNF induces SS mRNA. We observed that H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK and PI3K pathways.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21184749</pmid><doi>10.1016/j.brainres.2010.12.031</doi><tpages>13</tpages></addata></record> |
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| subjects | Animals antibodies BDNF Biological and medical sciences Blotting, Western brain Brain-Derived Neurotrophic Factor - antagonists & inhibitors Brain-Derived Neurotrophic Factor - pharmacology Cell physiology Cells, Cultured Cerebral Cortex - drug effects Cerebral Cortex - metabolism CREB-CRE Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Electric Stimulation Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Extracellular Signal-Regulated MAP Kinases - metabolism Female Fundamental and applied biological sciences. Psychology Gene Expression Immunoglobulin G - isolation & purification luciferase Mitogen-Activated Protein Kinases - antagonists & inhibitors Molecular and cellular biology Neurology neurons phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - antagonists & inhibitors Potassium - pharmacology Pregnancy promoter regions Rats Rats, Sprague-Dawley Regulatory Elements, Transcriptional reporter genes Responses to growth factors, tumor promotors, other factors RNA, Messenger - biosynthesis RNA, Messenger - genetics signal transduction Signal Transduction - drug effects Signaling pathway somatostatin Somatostatin - biosynthesis Somatostatin - genetics transcription (genetics) Transcription, Genetic - drug effects Transfection |
| title | Regulation of somatostatin gene expression by brain derived neurotrophic factor in fetal rat cerebrocortical cells |
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