Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells
We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gen...
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Veröffentlicht in: | Cell and tissue research 2011-08, Vol.345 (2), p.231-241 |
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creator | Irie, Yasuyuki Saeki, Makio Tanaka, Hidekazu Kanemura, Yonehiro Otake, Shinpei Ozono, Yoshiyuki Nagai, Toshisaburou Kondo, Yukiko Kudo, Kenzo Kamisaki, Yoshinori Miki, Naomasa Taira, Eiichi |
description | We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction. |
doi_str_mv | 10.1007/s00441-011-1207-5 |
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Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.</description><identifier>ISSN: 0302-766X</identifier><identifier>EISSN: 1432-0878</identifier><identifier>DOI: 10.1007/s00441-011-1207-5</identifier><identifier>PMID: 21789578</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Addiction ; Analysis ; Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; BiP protein ; Cell body ; Central nervous system ; CHOP protein ; Dopamine ; Dopamine - biosynthesis ; Dopamine Agents - pharmacology ; Dopaminergic Neurons - drug effects ; Dopaminergic Neurons - metabolism ; Endoplasmic reticulum ; Endoplasmic Reticulum - drug effects ; Gene Expression Regulation - drug effects ; Genes ; Human Genetics ; Immunofluorescence ; Methamphetamine ; Methamphetamine - toxicity ; Mice ; Microscopy ; Molecular Medicine ; Nervous system ; Neurons ; Polymerase chain reaction ; Proteins ; Proteomics ; Receptors, Dopamine D1 - metabolism ; Regular ; Regular Article ; Rodents ; Stress ; Substantia nigra ; Toxicity ; Transcription Factor CHOP - biosynthesis ; Transcription Factor CHOP - genetics ; Ventral tegmentum</subject><ispartof>Cell and tissue research, 2011-08, Vol.345 (2), p.231-241</ispartof><rights>The Author(s) 2011</rights><rights>COPYRIGHT 2011 Springer</rights><rights>Springer-Verlag 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c598t-de0c1e3552fbd0210c06f26568eaa0a970edbb53a4c1415d241902d3db79f7753</citedby><cites>FETCH-LOGICAL-c598t-de0c1e3552fbd0210c06f26568eaa0a970edbb53a4c1415d241902d3db79f7753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00441-011-1207-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00441-011-1207-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21789578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Irie, Yasuyuki</creatorcontrib><creatorcontrib>Saeki, Makio</creatorcontrib><creatorcontrib>Tanaka, Hidekazu</creatorcontrib><creatorcontrib>Kanemura, Yonehiro</creatorcontrib><creatorcontrib>Otake, Shinpei</creatorcontrib><creatorcontrib>Ozono, Yoshiyuki</creatorcontrib><creatorcontrib>Nagai, Toshisaburou</creatorcontrib><creatorcontrib>Kondo, Yukiko</creatorcontrib><creatorcontrib>Kudo, Kenzo</creatorcontrib><creatorcontrib>Kamisaki, Yoshinori</creatorcontrib><creatorcontrib>Miki, Naomasa</creatorcontrib><creatorcontrib>Taira, Eiichi</creatorcontrib><title>Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells</title><title>Cell and tissue research</title><addtitle>Cell Tissue Res</addtitle><addtitle>Cell Tissue Res</addtitle><description>We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.</description><subject>Addiction</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>BiP protein</subject><subject>Cell body</subject><subject>Central nervous system</subject><subject>CHOP protein</subject><subject>Dopamine</subject><subject>Dopamine - biosynthesis</subject><subject>Dopamine Agents - pharmacology</subject><subject>Dopaminergic Neurons - drug effects</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - drug effects</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes</subject><subject>Human Genetics</subject><subject>Immunofluorescence</subject><subject>Methamphetamine</subject><subject>Methamphetamine - toxicity</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Molecular Medicine</subject><subject>Nervous system</subject><subject>Neurons</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Regular</subject><subject>Regular Article</subject><subject>Rodents</subject><subject>Stress</subject><subject>Substantia nigra</subject><subject>Toxicity</subject><subject>Transcription Factor CHOP - biosynthesis</subject><subject>Transcription Factor CHOP - genetics</subject><subject>Ventral 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induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells</title><author>Irie, Yasuyuki ; Saeki, Makio ; Tanaka, Hidekazu ; Kanemura, Yonehiro ; Otake, Shinpei ; Ozono, Yoshiyuki ; Nagai, Toshisaburou ; Kondo, Yukiko ; Kudo, Kenzo ; Kamisaki, Yoshinori ; Miki, Naomasa ; Taira, Eiichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c598t-de0c1e3552fbd0210c06f26568eaa0a970edbb53a4c1415d241902d3db79f7753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Addiction</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>BiP protein</topic><topic>Cell body</topic><topic>Central nervous system</topic><topic>CHOP protein</topic><topic>Dopamine</topic><topic>Dopamine - biosynthesis</topic><topic>Dopamine Agents - pharmacology</topic><topic>Dopaminergic Neurons - drug effects</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - drug effects</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes</topic><topic>Human Genetics</topic><topic>Immunofluorescence</topic><topic>Methamphetamine</topic><topic>Methamphetamine - toxicity</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Molecular Medicine</topic><topic>Nervous system</topic><topic>Neurons</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Regular</topic><topic>Regular Article</topic><topic>Rodents</topic><topic>Stress</topic><topic>Substantia nigra</topic><topic>Toxicity</topic><topic>Transcription Factor CHOP - biosynthesis</topic><topic>Transcription Factor CHOP - genetics</topic><topic>Ventral 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Yoshinori</au><au>Miki, Naomasa</au><au>Taira, Eiichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells</atitle><jtitle>Cell and tissue research</jtitle><stitle>Cell Tissue Res</stitle><addtitle>Cell Tissue Res</addtitle><date>2011-08-01</date><risdate>2011</risdate><volume>345</volume><issue>2</issue><spage>231</spage><epage>241</epage><pages>231-241</pages><issn>0302-766X</issn><eissn>1432-0878</eissn><abstract>We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24–48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase of CHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21789578</pmid><doi>10.1007/s00441-011-1207-5</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Addiction Analysis Animals Apoptosis Biomedical and Life Sciences Biomedicine BiP protein Cell body Central nervous system CHOP protein Dopamine Dopamine - biosynthesis Dopamine Agents - pharmacology Dopaminergic Neurons - drug effects Dopaminergic Neurons - metabolism Endoplasmic reticulum Endoplasmic Reticulum - drug effects Gene Expression Regulation - drug effects Genes Human Genetics Immunofluorescence Methamphetamine Methamphetamine - toxicity Mice Microscopy Molecular Medicine Nervous system Neurons Polymerase chain reaction Proteins Proteomics Receptors, Dopamine D1 - metabolism Regular Regular Article Rodents Stress Substantia nigra Toxicity Transcription Factor CHOP - biosynthesis Transcription Factor CHOP - genetics Ventral tegmentum |
title | Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells |
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