Morphine Promotes Astrocyte‐Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε‐Dependent ERK Activation and TRBP Phosphorylation
Previously we have shown that morphine regulates adult neurogenesis by modulating miR‐181a maturation and subsequent hippocampal neural progenitor cell (NPC) lineages. Using NPCs cultured from PKCε or β‐arrestin2 knockout mice and the MAPK/ERK kinase inhibitor U0126, we demonstrate that regulation o...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2015-09, Vol.33 (9), p.2762-2772 |
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| creator | Xu, Chi Zheng, Hui Loh, Horace H. Law, Ping‐Yee |
| description | Previously we have shown that morphine regulates adult neurogenesis by modulating miR‐181a maturation and subsequent hippocampal neural progenitor cell (NPC) lineages. Using NPCs cultured from PKCε or β‐arrestin2 knockout mice and the MAPK/ERK kinase inhibitor U0126, we demonstrate that regulation of NPC differentiation via the miR‐181a/Prox1/Notch1 pathway exhibits ligand‐dependent selectivity. In NPCs, morphine and fentanyl activate ERK via the PKCε‐ and β‐arrestin‐dependent pathways, respectively. After fentanyl exposure, the activated phospho‐ERK translocates to the nucleus. Conversely, after morphine treatment, phospho‐ERK remains in the cytosol and is capable of phosphorylating TAR RNA‐binding protein (TRBP), a cofactor of Dicer. This augments Dicer activity and promotes the maturation of miR‐181a. Furthermore, using NPCs transfected with wild‐type TRBP, SΔA, and SΔD TRBP mutants, we confirmed the crucial role of TRBP phosphorylation in Dicer activity, miR‐181a maturation, and finally the morphine‐induced astrocyte‐preferential differentiation of NPCs. Thus, morphine modulates the lineage‐specific differentiation of NPCs by PKCε‐dependent ERK activation with subsequent TRBP phosphorylation and miR‐181a maturation. Stem Cells 2015;33:2762–2772 |
| doi_str_mv | 10.1002/stem.2055 |
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Using NPCs cultured from PKCε or β‐arrestin2 knockout mice and the MAPK/ERK kinase inhibitor U0126, we demonstrate that regulation of NPC differentiation via the miR‐181a/Prox1/Notch1 pathway exhibits ligand‐dependent selectivity. In NPCs, morphine and fentanyl activate ERK via the PKCε‐ and β‐arrestin‐dependent pathways, respectively. After fentanyl exposure, the activated phospho‐ERK translocates to the nucleus. Conversely, after morphine treatment, phospho‐ERK remains in the cytosol and is capable of phosphorylating TAR RNA‐binding protein (TRBP), a cofactor of Dicer. This augments Dicer activity and promotes the maturation of miR‐181a. Furthermore, using NPCs transfected with wild‐type TRBP, SΔA, and SΔD TRBP mutants, we confirmed the crucial role of TRBP phosphorylation in Dicer activity, miR‐181a maturation, and finally the morphine‐induced astrocyte‐preferential differentiation of NPCs. Thus, morphine modulates the lineage‐specific differentiation of NPCs by PKCε‐dependent ERK activation with subsequent TRBP phosphorylation and miR‐181a maturation. Stem Cells 2015;33:2762–2772</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.2055</identifier><identifier>PMID: 26012717</identifier><language>eng</language><publisher>United States</publisher><subject>Adult stem cells ; Animals ; Astrocytes - drug effects ; Astrocytes - metabolism ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Cell signaling ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - metabolism ; Male ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; MAPK ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; miRNA ; Morphine - pharmacology ; Neural differentiation ; Neural stem cell ; Neural Stem Cells - drug effects ; Neural Stem Cells - metabolism ; Phosphorylation - drug effects ; Progenitor cells ; Protein Kinase C-epsilon - metabolism ; RNA-Binding Proteins - metabolism ; Signal transduction</subject><ispartof>Stem cells (Dayton, Ohio), 2015-09, Vol.33 (9), p.2762-2772</ispartof><rights>2015 AlphaMed Press</rights><rights>2015 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5185-9b205d9f7658656bed050888c5df439d50162880017ce11b9ab9fda9357330c23</citedby><cites>FETCH-LOGICAL-c5185-9b205d9f7658656bed050888c5df439d50162880017ce11b9ab9fda9357330c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26012717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Chi</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><creatorcontrib>Loh, Horace H.</creatorcontrib><creatorcontrib>Law, Ping‐Yee</creatorcontrib><title>Morphine Promotes Astrocyte‐Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε‐Dependent ERK Activation and TRBP Phosphorylation</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Previously we have shown that morphine regulates adult neurogenesis by modulating miR‐181a maturation and subsequent hippocampal neural progenitor cell (NPC) lineages. Using NPCs cultured from PKCε or β‐arrestin2 knockout mice and the MAPK/ERK kinase inhibitor U0126, we demonstrate that regulation of NPC differentiation via the miR‐181a/Prox1/Notch1 pathway exhibits ligand‐dependent selectivity. In NPCs, morphine and fentanyl activate ERK via the PKCε‐ and β‐arrestin‐dependent pathways, respectively. After fentanyl exposure, the activated phospho‐ERK translocates to the nucleus. Conversely, after morphine treatment, phospho‐ERK remains in the cytosol and is capable of phosphorylating TAR RNA‐binding protein (TRBP), a cofactor of Dicer. This augments Dicer activity and promotes the maturation of miR‐181a. Furthermore, using NPCs transfected with wild‐type TRBP, SΔA, and SΔD TRBP mutants, we confirmed the crucial role of TRBP phosphorylation in Dicer activity, miR‐181a maturation, and finally the morphine‐induced astrocyte‐preferential differentiation of NPCs. Thus, morphine modulates the lineage‐specific differentiation of NPCs by PKCε‐dependent ERK activation with subsequent TRBP phosphorylation and miR‐181a maturation. Stem Cells 2015;33:2762–2772</description><subject>Adult stem cells</subject><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cell signaling</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>MAPK</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>miRNA</subject><subject>Morphine - pharmacology</subject><subject>Neural differentiation</subject><subject>Neural stem cell</subject><subject>Neural Stem Cells - drug effects</subject><subject>Neural Stem Cells - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Progenitor cells</subject><subject>Protein Kinase C-epsilon - metabolism</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Signal transduction</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1u1DAYhiMEoqVlwQWQl7BIayfx3wZpmA4takeNyrC2HOdLxyiJUzszaHYcgRNwi16DQ3ASPJ22ggUSK9v6Hj3y975J8orgI4JxdhxG6I4yTOmTZJ_QQqaFJOJpvGPGUoql3EtehPAFY1JQIZ4nexnDJOOE7yc_5s4PS9sDKr3r3AgBTcLondmM8Ovb99JDAx760eoWndjm4TFa1yPXoLlbBUBndhic0d0Qoai5ht6OzqMptG1Aa6tReT79eRt1JzBAX0cDml2do4kZ7Xqn0n2NFlfvS1QuXRiWzm_au8Fh8qzRbYCX9-dB8vnDbDE9Sy8uTz9OJxepoUTQVFZx-1o2nFHBKKugxhQLIQytmyKXNcWEZULEALgBQiqpK9nUWuaU5zk2WX6QvNt5h1XVQW3iF71u1eBtp_1GOW3V35PeLtW1W6sixk34VvDmXuDdzQrCqDobTAxA9xAzUoTHwJng7H9QzCgXlPCIvt2hxrsQYhePPyJYbatX2-rVtvrIvv5zhUfyoesIHO-Ar7aFzb9N6tNiNr9T_gZV6b7D</recordid><startdate>201509</startdate><enddate>201509</enddate><creator>Xu, Chi</creator><creator>Zheng, Hui</creator><creator>Loh, Horace H.</creator><creator>Law, Ping‐Yee</creator><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>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201509</creationdate><title>Morphine Promotes Astrocyte‐Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε‐Dependent ERK Activation and TRBP Phosphorylation</title><author>Xu, Chi ; Zheng, Hui ; Loh, Horace H. ; Law, Ping‐Yee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5185-9b205d9f7658656bed050888c5df439d50162880017ce11b9ab9fda9357330c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult stem cells</topic><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - physiology</topic><topic>Cell signaling</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>MAPK</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>miRNA</topic><topic>Morphine - pharmacology</topic><topic>Neural differentiation</topic><topic>Neural stem cell</topic><topic>Neural Stem Cells - drug effects</topic><topic>Neural Stem Cells - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Progenitor cells</topic><topic>Protein Kinase C-epsilon - metabolism</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Signal transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Chi</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><creatorcontrib>Loh, Horace H.</creatorcontrib><creatorcontrib>Law, Ping‐Yee</creatorcontrib><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>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Chi</au><au>Zheng, Hui</au><au>Loh, Horace H.</au><au>Law, Ping‐Yee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphine Promotes Astrocyte‐Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε‐Dependent ERK Activation and TRBP Phosphorylation</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2015-09</date><risdate>2015</risdate><volume>33</volume><issue>9</issue><spage>2762</spage><epage>2772</epage><pages>2762-2772</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Previously we have shown that morphine regulates adult neurogenesis by modulating miR‐181a maturation and subsequent hippocampal neural progenitor cell (NPC) lineages. Using NPCs cultured from PKCε or β‐arrestin2 knockout mice and the MAPK/ERK kinase inhibitor U0126, we demonstrate that regulation of NPC differentiation via the miR‐181a/Prox1/Notch1 pathway exhibits ligand‐dependent selectivity. In NPCs, morphine and fentanyl activate ERK via the PKCε‐ and β‐arrestin‐dependent pathways, respectively. After fentanyl exposure, the activated phospho‐ERK translocates to the nucleus. Conversely, after morphine treatment, phospho‐ERK remains in the cytosol and is capable of phosphorylating TAR RNA‐binding protein (TRBP), a cofactor of Dicer. This augments Dicer activity and promotes the maturation of miR‐181a. Furthermore, using NPCs transfected with wild‐type TRBP, SΔA, and SΔD TRBP mutants, we confirmed the crucial role of TRBP phosphorylation in Dicer activity, miR‐181a maturation, and finally the morphine‐induced astrocyte‐preferential differentiation of NPCs. Thus, morphine modulates the lineage‐specific differentiation of NPCs by PKCε‐dependent ERK activation with subsequent TRBP phosphorylation and miR‐181a maturation. Stem Cells 2015;33:2762–2772</abstract><cop>United States</cop><pmid>26012717</pmid><doi>10.1002/stem.2055</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adult stem cells Animals Astrocytes - drug effects Astrocytes - metabolism Cell Differentiation - drug effects Cell Differentiation - physiology Cell signaling Hippocampus - cytology Hippocampus - drug effects Hippocampus - metabolism Male MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology MAPK Mice Mice, Inbred C57BL Mice, Knockout miRNA Morphine - pharmacology Neural differentiation Neural stem cell Neural Stem Cells - drug effects Neural Stem Cells - metabolism Phosphorylation - drug effects Progenitor cells Protein Kinase C-epsilon - metabolism RNA-Binding Proteins - metabolism Signal transduction |
| title | Morphine Promotes Astrocyte‐Preferential Differentiation of Mouse Hippocampal Progenitor Cells via PKCε‐Dependent ERK Activation and TRBP Phosphorylation |
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