Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells
Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises n...
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creator | Melo, Zesergio Castillo, Ximena Moreno-Carranza, Bibiana Ledesma-Colunga, María G. Arnold, Edith López-Casillas, Fernando Ruíz-Herrera, Xarubet Clapp, Carmen Martínez de la Escalera, Gonzalo |
description | Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation. |
doi_str_mv | 10.1159/000499507 |
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Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation.</description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000499507</identifier><identifier>PMID: 31091528</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Cell differentiation ; Cell lines ; Composition ; Development and progression ; Health aspects ; Nerve growth factor ; Neurological research ; Original Paper ; Pheochromocytoma ; Prolactin</subject><ispartof>Neuroendocrinology, 2019-08, Vol.109 (2), p.152-164</ispartof><rights>2019 S. Karger AG, Basel</rights><rights>2019 S. Karger AG, Basel.</rights><rights>COPYRIGHT 2019 S. Karger AG</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-16bfa796e84b78e972eecaf13a8dd779f6ef27715911b88588b7944bd890812a3</citedby><cites>FETCH-LOGICAL-c407t-16bfa796e84b78e972eecaf13a8dd779f6ef27715911b88588b7944bd890812a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31091528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Melo, Zesergio</creatorcontrib><creatorcontrib>Castillo, Ximena</creatorcontrib><creatorcontrib>Moreno-Carranza, Bibiana</creatorcontrib><creatorcontrib>Ledesma-Colunga, María G.</creatorcontrib><creatorcontrib>Arnold, Edith</creatorcontrib><creatorcontrib>López-Casillas, Fernando</creatorcontrib><creatorcontrib>Ruíz-Herrera, Xarubet</creatorcontrib><creatorcontrib>Clapp, Carmen</creatorcontrib><creatorcontrib>Martínez de la Escalera, Gonzalo</creatorcontrib><title>Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells</title><title>Neuroendocrinology</title><addtitle>Neuroendocrinology</addtitle><description>Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation.</description><subject>Cell differentiation</subject><subject>Cell lines</subject><subject>Composition</subject><subject>Development and progression</subject><subject>Health aspects</subject><subject>Nerve growth factor</subject><subject>Neurological research</subject><subject>Original Paper</subject><subject>Pheochromocytoma</subject><subject>Prolactin</subject><issn>0028-3835</issn><issn>1423-0194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpt0c1rFDEYBvAgil2rB-8iAS96mJqPmUlyLKutC0WLVa9DJvNmNzqTrElmtf-9KbsuFMp7CITfE_LyIPSSkjNKG_WeEFIr1RDxCC1ozXhFqKofowUhTFZc8uYEPUvpZ2FMcfYUnXBKFG2YXCD_Q6fg_Mb1zuObebuNkBIk_BniDvBlDH_yBl9ok0OsVn6YDQz4g7MWIvjsdHbBY-2HEo07t9MjDhZfLynD1xsIZhPDFMxtDpPGSxjH9Bw9sXpM8OJwnqLvFx-_LT9VV18uV8vzq8rUROSKtr3VQrUg615IUIIBGG0p13IYhFC2BcuEKLtT2kvZSNkLVdf9IBWRlGl-it7u393G8HuGlLvJJVN-oD2EOXWMcUbKiLbQN3u61iN0ztuQozZ3vDtvOedNUxNS1NkDqswAkzPBg3Xl_l7g3b1AMRn-5rWeU-pWN18ftCaGlCLYbhvdpONtR0l313B3bLjY14fN5n6C4Sj_V1rAqz34peMa4hEc8v8A7MWnDw</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Melo, Zesergio</creator><creator>Castillo, Ximena</creator><creator>Moreno-Carranza, Bibiana</creator><creator>Ledesma-Colunga, María G.</creator><creator>Arnold, Edith</creator><creator>López-Casillas, Fernando</creator><creator>Ruíz-Herrera, Xarubet</creator><creator>Clapp, Carmen</creator><creator>Martínez de la Escalera, Gonzalo</creator><general>S. Karger AG</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>7X8</scope></search><sort><creationdate>20190801</creationdate><title>Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells</title><author>Melo, Zesergio ; Castillo, Ximena ; Moreno-Carranza, Bibiana ; Ledesma-Colunga, María G. ; Arnold, Edith ; López-Casillas, Fernando ; Ruíz-Herrera, Xarubet ; Clapp, Carmen ; Martínez de la Escalera, Gonzalo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-16bfa796e84b78e972eecaf13a8dd779f6ef27715911b88588b7944bd890812a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cell differentiation</topic><topic>Cell lines</topic><topic>Composition</topic><topic>Development and progression</topic><topic>Health aspects</topic><topic>Nerve growth factor</topic><topic>Neurological research</topic><topic>Original Paper</topic><topic>Pheochromocytoma</topic><topic>Prolactin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Melo, Zesergio</creatorcontrib><creatorcontrib>Castillo, Ximena</creatorcontrib><creatorcontrib>Moreno-Carranza, Bibiana</creatorcontrib><creatorcontrib>Ledesma-Colunga, María G.</creatorcontrib><creatorcontrib>Arnold, Edith</creatorcontrib><creatorcontrib>López-Casillas, Fernando</creatorcontrib><creatorcontrib>Ruíz-Herrera, Xarubet</creatorcontrib><creatorcontrib>Clapp, Carmen</creatorcontrib><creatorcontrib>Martínez de la Escalera, Gonzalo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Melo, Zesergio</au><au>Castillo, Ximena</au><au>Moreno-Carranza, Bibiana</au><au>Ledesma-Colunga, María G.</au><au>Arnold, Edith</au><au>López-Casillas, Fernando</au><au>Ruíz-Herrera, Xarubet</au><au>Clapp, Carmen</au><au>Martínez de la Escalera, Gonzalo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells</atitle><jtitle>Neuroendocrinology</jtitle><addtitle>Neuroendocrinology</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>109</volume><issue>2</issue><spage>152</spage><epage>164</epage><pages>152-164</pages><issn>0028-3835</issn><eissn>1423-0194</eissn><abstract>Background: Vasoinhibin, a protein derived from prolactin, regulates various vascular functions including endothelial cell survival. Of note, vasoinhibin is present in the central nervous system, where it triggers neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin compromises nerve growth factor (NGF)-induced neurite outgrowth in primary sensory neurons of the peripheral nervous system. Nonetheless, information on the functions of vasoinhibin in developing neurons remains limited. The present study explored whether vasoinhibin affects the neurotrophic actions of NGF by measuring the cell differentiation and survival of PC12 pheochromocytoma cells. Methods: The effects of recombinant or lentiviral vector-transduced human vasoinhibin were tested on differentiating PC12 cells. Neurite outgrowth was quantified by measuring their length and density. The MTT assay was employed to assess cell viability, and ELISA was used to quantify DNA fragmentation as an index of apoptosis. Phosphorylated Akt and ERK1/2 were analyzed by Western blotting. Results: The addition of a human recombinant vasoinhibin, and the transduction of a lentiviral vector carrying a human vasoinhibin sequence, significantly reduced NGF-induced neurite outgrowth, cell survival, and phosphorylation of Akt and ERK1/2, and increased DNA fragmentation and caspase 3 activation in PC12 cells. Conclusions: Vasoinhibin downregulates NGF-induced differentiation and survival of PC12 cells, blocking tropomyosin receptor kinase A-triggered signaling pathways and increasing apoptosis. These results establish that vasoinhibin interaction with NGF and other neurotrophins may be critical in mediating pathways involved in neuronal survival and differentiation.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>31091528</pmid><doi>10.1159/000499507</doi><tpages>13</tpages></addata></record> |
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subjects | Cell differentiation Cell lines Composition Development and progression Health aspects Nerve growth factor Neurological research Original Paper Pheochromocytoma Prolactin |
title | Vasoinhibin Suppresses Nerve Growth Factor-Induced Differentiation and Survival of PC12 Pheochromocytoma Cells |
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