Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation
Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neuroprotective effects of neurotrophic factors against ethanol toxicity. Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growt...
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Veröffentlicht in: | Neuroscience letters 2000-09, Vol.291 (2), p.121-125 |
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description | Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neuroprotective effects of neurotrophic factors against ethanol toxicity. Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol+NGF or BDNF, the PI3-K inhibitor wortmannin (10 or 100 μM), and wortmannin+ethanol+NGF or BDNF. Neuronal survival was determined via the MTT assay. The results indicated that both NGF and BDNF ameliorate ethanol neurotoxicity, and wortmannin abolished this effect, except at the higher ethanol concentration combined with the lower wortmannin level. These data strongly implicate the PI3-K pathway in growth factor protection against ethanol neurotoxicity. |
doi_str_mv | 10.1016/S0304-3940(00)01398-7 |
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Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol+NGF or BDNF, the PI3-K inhibitor wortmannin (10 or 100 μM), and wortmannin+ethanol+NGF or BDNF. Neuronal survival was determined via the MTT assay. The results indicated that both NGF and BDNF ameliorate ethanol neurotoxicity, and wortmannin abolished this effect, except at the higher ethanol concentration combined with the lower wortmannin level. These data strongly implicate the PI3-K pathway in growth factor protection against ethanol neurotoxicity.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/S0304-3940(00)01398-7</identifier><identifier>PMID: 10978589</identifier><identifier>CODEN: NELED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Androstadienes - pharmacology ; Animals ; Biological and medical sciences ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - pharmacology ; Cells, Cultured ; Cerebellum - cytology ; Cerebellum - drug effects ; Cerebellum - enzymology ; Cytoplasmic Granules - drug effects ; Cytoplasmic Granules - enzymology ; Enzyme Activation - drug effects ; Ethanol ; Ethanol - antagonists & inhibitors ; Ethanol - toxicity ; Fetal alcohol syndrome ; Granule cells ; Male ; Medical sciences ; Nerve growth factor ; Nerve Growth Factor - metabolism ; Neuropharmacology ; Neuroprotection ; Neuroprotective agent ; Neuroprotective Agents - pharmacology ; Pharmacology. Drug treatments ; Phosphatidylinositol 3-kinase ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; Rats ; Rats, Long-Evans ; Wortmannin</subject><ispartof>Neuroscience letters, 2000-09, Vol.291 (2), p.121-125</ispartof><rights>2000 Elsevier Science Ireland Ltd</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-d2e33eb4c886e1d560309e96c37363b5c671870b0bd2a6d5229c3aa0e862bc2e3</citedby><cites>FETCH-LOGICAL-c421t-d2e33eb4c886e1d560309e96c37363b5c671870b0bd2a6d5229c3aa0e862bc2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0304-3940(00)01398-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1505458$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10978589$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heaton, Marieta Barrow</creatorcontrib><creatorcontrib>Kim, Danny S</creatorcontrib><creatorcontrib>Paiva, Michael</creatorcontrib><title>Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neuroprotective effects of neurotrophic factors against ethanol toxicity. Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol+NGF or BDNF, the PI3-K inhibitor wortmannin (10 or 100 μM), and wortmannin+ethanol+NGF or BDNF. Neuronal survival was determined via the MTT assay. The results indicated that both NGF and BDNF ameliorate ethanol neurotoxicity, and wortmannin abolished this effect, except at the higher ethanol concentration combined with the lower wortmannin level. These data strongly implicate the PI3-K pathway in growth factor protection against ethanol neurotoxicity.</description><subject>Androstadienes - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - pharmacology</subject><subject>Cells, Cultured</subject><subject>Cerebellum - cytology</subject><subject>Cerebellum - drug effects</subject><subject>Cerebellum - enzymology</subject><subject>Cytoplasmic Granules - drug effects</subject><subject>Cytoplasmic Granules - enzymology</subject><subject>Enzyme Activation - drug effects</subject><subject>Ethanol</subject><subject>Ethanol - antagonists & inhibitors</subject><subject>Ethanol - toxicity</subject><subject>Fetal alcohol syndrome</subject><subject>Granule cells</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nerve growth factor</subject><subject>Nerve Growth Factor - metabolism</subject><subject>Neuropharmacology</subject><subject>Neuroprotection</subject><subject>Neuroprotective agent</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphatidylinositol 3-kinase</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Wortmannin</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O1DAMgCMEYoeFRwDlgBAcCk7TNO1phVb8SSs4AOfITT07gUzTTdIV8xi8MSkzAm5IkRJZn2P7M2OPBbwUINpXn0FCU8m-gecAL0DIvqv0HbYRna4r3ev6Ltv8Qc7Yg5S-AYASqrnPzgT0ulNdv2E_P9ISQ45h3jnLt2hziHwuEbLZhYnjNbopZU55h1PwPIcfzrp84G7iETO3FGkg7zHy64jT4qmEvOd28XmJlHikm8Wtj3kX0rzD7MaDd1NILpfvZPXdTZiIl8LuFteSD9m9LfpEj073Ofv69s2Xy_fV1ad3Hy5fX1W2qUWuxpqkpKGxXdeSGFVbhu2pb63UspWDsq0uKmCAYayxHVVd91YiAnVtPdiSfM6eHf8t094slLLZu7T2jhOFJRmhNawCC6iOoI0hpUhbM0e3x3gwAsy6C_N7F2YVbaCcdRdGl7wnpwLLsKfxn6yj_AI8PQGYLPpt8Wdd-sspUI3qCnZxxKjYuHUUTbKOJktj8WqzGYP7Tye_AI_aqhI</recordid><startdate>20000915</startdate><enddate>20000915</enddate><creator>Heaton, Marieta Barrow</creator><creator>Kim, Danny S</creator><creator>Paiva, Michael</creator><general>Elsevier Ireland Ltd</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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20000915</creationdate><title>Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation</title><author>Heaton, Marieta Barrow ; Kim, Danny S ; Paiva, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-d2e33eb4c886e1d560309e96c37363b5c671870b0bd2a6d5229c3aa0e862bc2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Androstadienes - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - pharmacology</topic><topic>Cells, Cultured</topic><topic>Cerebellum - cytology</topic><topic>Cerebellum - drug effects</topic><topic>Cerebellum - enzymology</topic><topic>Cytoplasmic Granules - drug effects</topic><topic>Cytoplasmic Granules - enzymology</topic><topic>Enzyme Activation - drug effects</topic><topic>Ethanol</topic><topic>Ethanol - antagonists & inhibitors</topic><topic>Ethanol - toxicity</topic><topic>Fetal alcohol syndrome</topic><topic>Granule cells</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nerve growth factor</topic><topic>Nerve Growth Factor - metabolism</topic><topic>Neuropharmacology</topic><topic>Neuroprotection</topic><topic>Neuroprotective agent</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphatidylinositol 3-kinase</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Wortmannin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heaton, Marieta Barrow</creatorcontrib><creatorcontrib>Kim, Danny S</creatorcontrib><creatorcontrib>Paiva, Michael</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>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heaton, Marieta Barrow</au><au>Kim, Danny S</au><au>Paiva, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2000-09-15</date><risdate>2000</risdate><volume>291</volume><issue>2</issue><spage>121</spage><epage>125</epage><pages>121-125</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><coden>NELED5</coden><abstract>Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neuroprotective effects of neurotrophic factors against ethanol toxicity. Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol+NGF or BDNF, the PI3-K inhibitor wortmannin (10 or 100 μM), and wortmannin+ethanol+NGF or BDNF. Neuronal survival was determined via the MTT assay. The results indicated that both NGF and BDNF ameliorate ethanol neurotoxicity, and wortmannin abolished this effect, except at the higher ethanol concentration combined with the lower wortmannin level. These data strongly implicate the PI3-K pathway in growth factor protection against ethanol neurotoxicity.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>10978589</pmid><doi>10.1016/S0304-3940(00)01398-7</doi><tpages>5</tpages></addata></record> |
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subjects | Androstadienes - pharmacology Animals Biological and medical sciences Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - pharmacology Cells, Cultured Cerebellum - cytology Cerebellum - drug effects Cerebellum - enzymology Cytoplasmic Granules - drug effects Cytoplasmic Granules - enzymology Enzyme Activation - drug effects Ethanol Ethanol - antagonists & inhibitors Ethanol - toxicity Fetal alcohol syndrome Granule cells Male Medical sciences Nerve growth factor Nerve Growth Factor - metabolism Neuropharmacology Neuroprotection Neuroprotective agent Neuroprotective Agents - pharmacology Pharmacology. Drug treatments Phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Rats Rats, Long-Evans Wortmannin |
title | Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation |
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