Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells
beta-Carbolines structurally related to the selective dopaminergic neurotoxin 1-methyl-4- phenylpyridinium (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease. The chloral-derived mammalian alkaloid derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaC...
Gespeichert in:
| Veröffentlicht in: | Journal of Neural Transmission 2006-12, Vol.113 (12), p.1895-1901 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1901 |
|---|---|
| container_issue | 12 |
| container_start_page | 1895 |
| container_title | Journal of Neural Transmission |
| container_volume | 113 |
| creator | Storch, A Hwang, Y-I Bringmann, G Feineis, D Ott, S Brückner, R Schwarz, J |
| description | beta-Carbolines structurally related to the selective dopaminergic neurotoxin 1-methyl-4- phenylpyridinium (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease. The chloral-derived mammalian alkaloid derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is formed endogenously by a Pictet-Spengler condensation from the biogenic amine tryptamine (Ta) and the hypnotic aldehyde chloral (Clo). Here we examine the dopaminergic toxicity of TaClo and related compounds by testing their differential cytotoxicities in dopaminergic SH-SY5Y and non-dopaminergic murine Neuro2A neuroblastoma cell lines as well as in heterologous expression systems of the dopamine transporter (DAT) using both HEK-293 and Neuro2A cells. All TaClo derivatives showed significant cytotoxicity in all cell lines after 72 hours with the following rank order of toxic potency: 1-Tribromomethyl-1,2,3,4-tetrahydro-beta-carboline (TaBro) > TaClo > MPP(+) > 1,2,3,4-tetrahydro-beta-carboline (THbetaC) > 2[N]-methyl-TaClo > 2[N]-methyl-THbetaC. In contrast to MPP(+), there was no selectivity towards dopaminergic cells or cells ectopically expressing the DAT in vitro. Our results suggest that TaClo and related analogs are strong cytotoxins without selectivity towards dopaminergic cells. |
| doi_str_mv | 10.1007/s00702-006-0495-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_19567364</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19567364</sourcerecordid><originalsourceid>FETCH-LOGICAL-c330t-8f76ca3d112cae3e3d74cdf5f5f076a6c3e5d10c47224325e747cc45ba2430b33</originalsourceid><addsrcrecordid>eNpFkE1LAzEQhoMoWqs_wIvsyVt0svnaHqX4BQUveg7ZJFsj282aZNX-e1NakIEZZuZ9h-FB6IrALQGQd6kkqDGAwMAWHPMjNCOMckyYoMdoBhQAL7hgZ-g8pU8AIEQ2p-iMiEY0csFnaL3c5pDDrzc-b6vQVeajD1H32Lrov52tWpc1Njq2ofeDS5VP1RBylUZnfOdNlcOPjrYM3RTDoPuyjZUNo94UeVwXhXF9ny7QSaf75C4PdY7eHx_els949fr0srxfYUMpZNx0UhhNLSG10Y46aiUztuMlQAotDHXcEjBM1jWjNXeSSWMYb3VpoaV0jm72d8cYviaXstr4tPtADy5MSZGCQ1LBipDshSaGlKLr1Bj9RsetIqB2dNWerip01Y6u4sVzfTg-tRtn_x0HnPQPkZ13ag</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19567364</pqid></control><display><type>article</type><title>Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Storch, A ; Hwang, Y-I ; Bringmann, G ; Feineis, D ; Ott, S ; Brückner, R ; Schwarz, J</creator><creatorcontrib>Storch, A ; Hwang, Y-I ; Bringmann, G ; Feineis, D ; Ott, S ; Brückner, R ; Schwarz, J</creatorcontrib><description>beta-Carbolines structurally related to the selective dopaminergic neurotoxin 1-methyl-4- phenylpyridinium (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease. The chloral-derived mammalian alkaloid derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is formed endogenously by a Pictet-Spengler condensation from the biogenic amine tryptamine (Ta) and the hypnotic aldehyde chloral (Clo). Here we examine the dopaminergic toxicity of TaClo and related compounds by testing their differential cytotoxicities in dopaminergic SH-SY5Y and non-dopaminergic murine Neuro2A neuroblastoma cell lines as well as in heterologous expression systems of the dopamine transporter (DAT) using both HEK-293 and Neuro2A cells. All TaClo derivatives showed significant cytotoxicity in all cell lines after 72 hours with the following rank order of toxic potency: 1-Tribromomethyl-1,2,3,4-tetrahydro-beta-carboline (TaBro) > TaClo > MPP(+) > 1,2,3,4-tetrahydro-beta-carboline (THbetaC) > 2[N]-methyl-TaClo > 2[N]-methyl-THbetaC. In contrast to MPP(+), there was no selectivity towards dopaminergic cells or cells ectopically expressing the DAT in vitro. Our results suggest that TaClo and related analogs are strong cytotoxins without selectivity towards dopaminergic cells.</description><identifier>ISSN: 0300-9564</identifier><identifier>EISSN: 1435-1463</identifier><identifier>DOI: 10.1007/s00702-006-0495-5</identifier><identifier>PMID: 16868795</identifier><language>eng</language><publisher>Austria</publisher><subject>1-Methyl-4-phenylpyridinium - toxicity ; Animals ; Brain Neoplasms - pathology ; Carbolines - toxicity ; Cell Line, Tumor ; Cell Survival - drug effects ; Data Interpretation, Statistical ; Dopamine - physiology ; Dopamine Agents - toxicity ; Dopamine Plasma Membrane Transport Proteins - metabolism ; Humans ; Mice ; MPTP Poisoning - pathology ; Neuroblastoma - pathology ; Neurons - drug effects ; Neurons - pathology ; Piperazines - pharmacology</subject><ispartof>Journal of Neural Transmission, 2006-12, Vol.113 (12), p.1895-1901</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c330t-8f76ca3d112cae3e3d74cdf5f5f076a6c3e5d10c47224325e747cc45ba2430b33</citedby><cites>FETCH-LOGICAL-c330t-8f76ca3d112cae3e3d74cdf5f5f076a6c3e5d10c47224325e747cc45ba2430b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16868795$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Storch, A</creatorcontrib><creatorcontrib>Hwang, Y-I</creatorcontrib><creatorcontrib>Bringmann, G</creatorcontrib><creatorcontrib>Feineis, D</creatorcontrib><creatorcontrib>Ott, S</creatorcontrib><creatorcontrib>Brückner, R</creatorcontrib><creatorcontrib>Schwarz, J</creatorcontrib><title>Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells</title><title>Journal of Neural Transmission</title><addtitle>J Neural Transm (Vienna)</addtitle><description>beta-Carbolines structurally related to the selective dopaminergic neurotoxin 1-methyl-4- phenylpyridinium (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease. The chloral-derived mammalian alkaloid derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is formed endogenously by a Pictet-Spengler condensation from the biogenic amine tryptamine (Ta) and the hypnotic aldehyde chloral (Clo). Here we examine the dopaminergic toxicity of TaClo and related compounds by testing their differential cytotoxicities in dopaminergic SH-SY5Y and non-dopaminergic murine Neuro2A neuroblastoma cell lines as well as in heterologous expression systems of the dopamine transporter (DAT) using both HEK-293 and Neuro2A cells. All TaClo derivatives showed significant cytotoxicity in all cell lines after 72 hours with the following rank order of toxic potency: 1-Tribromomethyl-1,2,3,4-tetrahydro-beta-carboline (TaBro) > TaClo > MPP(+) > 1,2,3,4-tetrahydro-beta-carboline (THbetaC) > 2[N]-methyl-TaClo > 2[N]-methyl-THbetaC. In contrast to MPP(+), there was no selectivity towards dopaminergic cells or cells ectopically expressing the DAT in vitro. Our results suggest that TaClo and related analogs are strong cytotoxins without selectivity towards dopaminergic cells.</description><subject>1-Methyl-4-phenylpyridinium - toxicity</subject><subject>Animals</subject><subject>Brain Neoplasms - pathology</subject><subject>Carbolines - toxicity</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Data Interpretation, Statistical</subject><subject>Dopamine - physiology</subject><subject>Dopamine Agents - toxicity</subject><subject>Dopamine Plasma Membrane Transport Proteins - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>MPTP Poisoning - pathology</subject><subject>Neuroblastoma - pathology</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Piperazines - pharmacology</subject><issn>0300-9564</issn><issn>1435-1463</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LAzEQhoMoWqs_wIvsyVt0svnaHqX4BQUveg7ZJFsj282aZNX-e1NakIEZZuZ9h-FB6IrALQGQd6kkqDGAwMAWHPMjNCOMckyYoMdoBhQAL7hgZ-g8pU8AIEQ2p-iMiEY0csFnaL3c5pDDrzc-b6vQVeajD1H32Lrov52tWpc1Njq2ofeDS5VP1RBylUZnfOdNlcOPjrYM3RTDoPuyjZUNo94UeVwXhXF9ny7QSaf75C4PdY7eHx_els949fr0srxfYUMpZNx0UhhNLSG10Y46aiUztuMlQAotDHXcEjBM1jWjNXeSSWMYb3VpoaV0jm72d8cYviaXstr4tPtADy5MSZGCQ1LBipDshSaGlKLr1Bj9RsetIqB2dNWerip01Y6u4sVzfTg-tRtn_x0HnPQPkZ13ag</recordid><startdate>20061201</startdate><enddate>20061201</enddate><creator>Storch, A</creator><creator>Hwang, Y-I</creator><creator>Bringmann, G</creator><creator>Feineis, D</creator><creator>Ott, S</creator><creator>Brückner, R</creator><creator>Schwarz, J</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>7TK</scope></search><sort><creationdate>20061201</creationdate><title>Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells</title><author>Storch, A ; Hwang, Y-I ; Bringmann, G ; Feineis, D ; Ott, S ; Brückner, R ; Schwarz, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-8f76ca3d112cae3e3d74cdf5f5f076a6c3e5d10c47224325e747cc45ba2430b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>1-Methyl-4-phenylpyridinium - toxicity</topic><topic>Animals</topic><topic>Brain Neoplasms - pathology</topic><topic>Carbolines - toxicity</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Data Interpretation, Statistical</topic><topic>Dopamine - physiology</topic><topic>Dopamine Agents - toxicity</topic><topic>Dopamine Plasma Membrane Transport Proteins - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>MPTP Poisoning - pathology</topic><topic>Neuroblastoma - pathology</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Piperazines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Storch, A</creatorcontrib><creatorcontrib>Hwang, Y-I</creatorcontrib><creatorcontrib>Bringmann, G</creatorcontrib><creatorcontrib>Feineis, D</creatorcontrib><creatorcontrib>Ott, S</creatorcontrib><creatorcontrib>Brückner, R</creatorcontrib><creatorcontrib>Schwarz, J</creatorcontrib><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><jtitle>Journal of Neural Transmission</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Storch, A</au><au>Hwang, Y-I</au><au>Bringmann, G</au><au>Feineis, D</au><au>Ott, S</au><au>Brückner, R</au><au>Schwarz, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells</atitle><jtitle>Journal of Neural Transmission</jtitle><addtitle>J Neural Transm (Vienna)</addtitle><date>2006-12-01</date><risdate>2006</risdate><volume>113</volume><issue>12</issue><spage>1895</spage><epage>1901</epage><pages>1895-1901</pages><issn>0300-9564</issn><eissn>1435-1463</eissn><abstract>beta-Carbolines structurally related to the selective dopaminergic neurotoxin 1-methyl-4- phenylpyridinium (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease. The chloral-derived mammalian alkaloid derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is formed endogenously by a Pictet-Spengler condensation from the biogenic amine tryptamine (Ta) and the hypnotic aldehyde chloral (Clo). Here we examine the dopaminergic toxicity of TaClo and related compounds by testing their differential cytotoxicities in dopaminergic SH-SY5Y and non-dopaminergic murine Neuro2A neuroblastoma cell lines as well as in heterologous expression systems of the dopamine transporter (DAT) using both HEK-293 and Neuro2A cells. All TaClo derivatives showed significant cytotoxicity in all cell lines after 72 hours with the following rank order of toxic potency: 1-Tribromomethyl-1,2,3,4-tetrahydro-beta-carboline (TaBro) > TaClo > MPP(+) > 1,2,3,4-tetrahydro-beta-carboline (THbetaC) > 2[N]-methyl-TaClo > 2[N]-methyl-THbetaC. In contrast to MPP(+), there was no selectivity towards dopaminergic cells or cells ectopically expressing the DAT in vitro. Our results suggest that TaClo and related analogs are strong cytotoxins without selectivity towards dopaminergic cells.</abstract><cop>Austria</cop><pmid>16868795</pmid><doi>10.1007/s00702-006-0495-5</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0300-9564 |
| ispartof | Journal of Neural Transmission, 2006-12, Vol.113 (12), p.1895-1901 |
| issn | 0300-9564 1435-1463 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19567364 |
| source | MEDLINE; SpringerLink Journals |
| subjects | 1-Methyl-4-phenylpyridinium - toxicity Animals Brain Neoplasms - pathology Carbolines - toxicity Cell Line, Tumor Cell Survival - drug effects Data Interpretation, Statistical Dopamine - physiology Dopamine Agents - toxicity Dopamine Plasma Membrane Transport Proteins - metabolism Humans Mice MPTP Poisoning - pathology Neuroblastoma - pathology Neurons - drug effects Neurons - pathology Piperazines - pharmacology |
| title | Cytotoxicity of chloral-derived beta-carbolines is not specific towards neuronal nor dopaminergic cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T03%3A20%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytotoxicity%20of%20chloral-derived%20beta-carbolines%20is%20not%20specific%20towards%20neuronal%20nor%20dopaminergic%20cells&rft.jtitle=Journal%20of%20Neural%20Transmission&rft.au=Storch,%20A&rft.date=2006-12-01&rft.volume=113&rft.issue=12&rft.spage=1895&rft.epage=1901&rft.pages=1895-1901&rft.issn=0300-9564&rft.eissn=1435-1463&rft_id=info:doi/10.1007/s00702-006-0495-5&rft_dat=%3Cproquest_cross%3E19567364%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=19567364&rft_id=info:pmid/16868795&rfr_iscdi=true |