4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro
Abstract The translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been inve...
Gespeichert in:
| Veröffentlicht in: | Brain research 2016-02, Vol.1632, p.91-97 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 97 |
|---|---|
| container_issue | |
| container_start_page | 91 |
| container_title | Brain research |
| container_volume | 1632 |
| creator | Arbo, B.D Marques, C.V Ruiz-Palmero, I Ortiz-Rodriguez, A Ghorbanpoor, S Arevalo, M.A Garcia-Segura, L.M Ribeiro, M.F |
| description | Abstract The translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of 4′-chlorodiazepam (4′-CD), a ligand of TSPO, against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells and its mechanisms of action. Aβ decreased the viability of SHSY-5Y neuroblastoma cells, while 4′-CD had a neuroprotective effect at the doses of 1 nM and 10 nM. The neuroprotective effects of 4′-CD against Aβ were associated with the inhibition of Aβ-induced upregulation of Bax and downregulation of survivin. In summary, our findings indicate that 4′-CD is neuroprotective against Aβ-induced neurotoxicity by a mechanism that may involve the regulation of Bax and survivin expression. |
| doi_str_mv | 10.1016/j.brainres.2015.12.018 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1765980470</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006899315009579</els_id><sourcerecordid>1765980470</sourcerecordid><originalsourceid>FETCH-LOGICAL-c504t-dcd40cc4371ad260bb8add4ede7cd1d682a71c64ef9856ffa74dcdea0e4ab7f83</originalsourceid><addsrcrecordid>eNqFks1u1DAUhS0EokPhFSov2SRcJ46dbBBoVApSJRbA2nLsm46HJB7sJOqwQjxSH4knwWFaFmxYXR3pnPvz6RJywSBnwMSrfd4G7caAMS-AVTkrcmD1I7JhtSwyUXB4TDYAILK6acoz8izGfZJl2cBTclYICbKRYkN-8l8_7rLtrvfBW6e_40EP1EU64hz8IfgJzeQWpPomTYsT1cOx985mLU6aTrvg55tdqkgHb-deT86P1Hc0zmFxixupHi1t9S390yppvD2kneNqS2pxU_DPyZNO9xFf3Ndz8uXd5eft--z649WH7dvrzFTAp8way8EYXkqmbSGgbWttLUeL0lhmRV1oyYzg2DV1JbpOS54iqAG5bmVXl-fk5alv2uXbjHFSg4sG-16P6OeomBRVUwOXkKziZDXBxxiwU4fgBh2OioFa-au9euCvVv6KFSrxT8GL-xlzO6D9G3sAngxvTgZMly4Og4rG4WjQupBQK-vd_2e8_qeF6d3ojO6_4hHj3s9hTBwVUzEF1Kf1C9YnYBVAU8mm_A26hLU2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1765980470</pqid></control><display><type>article</type><title>4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Arbo, B.D ; Marques, C.V ; Ruiz-Palmero, I ; Ortiz-Rodriguez, A ; Ghorbanpoor, S ; Arevalo, M.A ; Garcia-Segura, L.M ; Ribeiro, M.F</creator><creatorcontrib>Arbo, B.D ; Marques, C.V ; Ruiz-Palmero, I ; Ortiz-Rodriguez, A ; Ghorbanpoor, S ; Arevalo, M.A ; Garcia-Segura, L.M ; Ribeiro, M.F</creatorcontrib><description>Abstract The translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of 4′-chlorodiazepam (4′-CD), a ligand of TSPO, against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells and its mechanisms of action. Aβ decreased the viability of SHSY-5Y neuroblastoma cells, while 4′-CD had a neuroprotective effect at the doses of 1 nM and 10 nM. The neuroprotective effects of 4′-CD against Aβ were associated with the inhibition of Aβ-induced upregulation of Bax and downregulation of survivin. In summary, our findings indicate that 4′-CD is neuroprotective against Aβ-induced neurotoxicity by a mechanism that may involve the regulation of Bax and survivin expression.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2015.12.018</identifier><identifier>PMID: 26707976</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alzheimer׳s disease ; Amyloid beta-Peptides - toxicity ; Apoptosis ; bcl-2-Associated X Protein - biosynthesis ; Benzodiazepinones - pharmacology ; Cell Line, Tumor ; Cell Survival - drug effects ; Cell Survival - physiology ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation ; Humans ; Inhibitor of Apoptosis Proteins - biosynthesis ; Neurology ; Neuroprotective Agents - pharmacology ; Peptide Fragments - toxicity ; Steroidogenesis ; Steroids ; Translocator protein (TSPO)</subject><ispartof>Brain research, 2016-02, Vol.1632, p.91-97</ispartof><rights>Elsevier B.V.</rights><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-dcd40cc4371ad260bb8add4ede7cd1d682a71c64ef9856ffa74dcdea0e4ab7f83</citedby><cites>FETCH-LOGICAL-c504t-dcd40cc4371ad260bb8add4ede7cd1d682a71c64ef9856ffa74dcdea0e4ab7f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899315009579$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26707976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arbo, B.D</creatorcontrib><creatorcontrib>Marques, C.V</creatorcontrib><creatorcontrib>Ruiz-Palmero, I</creatorcontrib><creatorcontrib>Ortiz-Rodriguez, A</creatorcontrib><creatorcontrib>Ghorbanpoor, S</creatorcontrib><creatorcontrib>Arevalo, M.A</creatorcontrib><creatorcontrib>Garcia-Segura, L.M</creatorcontrib><creatorcontrib>Ribeiro, M.F</creatorcontrib><title>4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract The translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of 4′-chlorodiazepam (4′-CD), a ligand of TSPO, against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells and its mechanisms of action. Aβ decreased the viability of SHSY-5Y neuroblastoma cells, while 4′-CD had a neuroprotective effect at the doses of 1 nM and 10 nM. The neuroprotective effects of 4′-CD against Aβ were associated with the inhibition of Aβ-induced upregulation of Bax and downregulation of survivin. In summary, our findings indicate that 4′-CD is neuroprotective against Aβ-induced neurotoxicity by a mechanism that may involve the regulation of Bax and survivin expression.</description><subject>Alzheimer׳s disease</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Apoptosis</subject><subject>bcl-2-Associated X Protein - biosynthesis</subject><subject>Benzodiazepinones - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - biosynthesis</subject><subject>Neurology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Peptide Fragments - toxicity</subject><subject>Steroidogenesis</subject><subject>Steroids</subject><subject>Translocator protein (TSPO)</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhS0EokPhFSov2SRcJ46dbBBoVApSJRbA2nLsm46HJB7sJOqwQjxSH4knwWFaFmxYXR3pnPvz6RJywSBnwMSrfd4G7caAMS-AVTkrcmD1I7JhtSwyUXB4TDYAILK6acoz8izGfZJl2cBTclYICbKRYkN-8l8_7rLtrvfBW6e_40EP1EU64hz8IfgJzeQWpPomTYsT1cOx985mLU6aTrvg55tdqkgHb-deT86P1Hc0zmFxixupHi1t9S390yppvD2kneNqS2pxU_DPyZNO9xFf3Ndz8uXd5eft--z649WH7dvrzFTAp8way8EYXkqmbSGgbWttLUeL0lhmRV1oyYzg2DV1JbpOS54iqAG5bmVXl-fk5alv2uXbjHFSg4sG-16P6OeomBRVUwOXkKziZDXBxxiwU4fgBh2OioFa-au9euCvVv6KFSrxT8GL-xlzO6D9G3sAngxvTgZMly4Og4rG4WjQupBQK-vd_2e8_qeF6d3ojO6_4hHj3s9hTBwVUzEF1Kf1C9YnYBVAU8mm_A26hLU2</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Arbo, B.D</creator><creator>Marques, C.V</creator><creator>Ruiz-Palmero, I</creator><creator>Ortiz-Rodriguez, A</creator><creator>Ghorbanpoor, S</creator><creator>Arevalo, M.A</creator><creator>Garcia-Segura, L.M</creator><creator>Ribeiro, M.F</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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></search><sort><creationdate>20160201</creationdate><title>4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro</title><author>Arbo, B.D ; Marques, C.V ; Ruiz-Palmero, I ; Ortiz-Rodriguez, A ; Ghorbanpoor, S ; Arevalo, M.A ; Garcia-Segura, L.M ; Ribeiro, M.F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-dcd40cc4371ad260bb8add4ede7cd1d682a71c64ef9856ffa74dcdea0e4ab7f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alzheimer׳s disease</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Apoptosis</topic><topic>bcl-2-Associated X Protein - biosynthesis</topic><topic>Benzodiazepinones - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins - biosynthesis</topic><topic>Neurology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Peptide Fragments - toxicity</topic><topic>Steroidogenesis</topic><topic>Steroids</topic><topic>Translocator protein (TSPO)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arbo, B.D</creatorcontrib><creatorcontrib>Marques, C.V</creatorcontrib><creatorcontrib>Ruiz-Palmero, I</creatorcontrib><creatorcontrib>Ortiz-Rodriguez, A</creatorcontrib><creatorcontrib>Ghorbanpoor, S</creatorcontrib><creatorcontrib>Arevalo, M.A</creatorcontrib><creatorcontrib>Garcia-Segura, L.M</creatorcontrib><creatorcontrib>Ribeiro, M.F</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arbo, B.D</au><au>Marques, C.V</au><au>Ruiz-Palmero, I</au><au>Ortiz-Rodriguez, A</au><au>Ghorbanpoor, S</au><au>Arevalo, M.A</au><au>Garcia-Segura, L.M</au><au>Ribeiro, M.F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>1632</volume><spage>91</spage><epage>97</epage><pages>91-97</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>Abstract The translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of 4′-chlorodiazepam (4′-CD), a ligand of TSPO, against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells and its mechanisms of action. Aβ decreased the viability of SHSY-5Y neuroblastoma cells, while 4′-CD had a neuroprotective effect at the doses of 1 nM and 10 nM. The neuroprotective effects of 4′-CD against Aβ were associated with the inhibition of Aβ-induced upregulation of Bax and downregulation of survivin. In summary, our findings indicate that 4′-CD is neuroprotective against Aβ-induced neurotoxicity by a mechanism that may involve the regulation of Bax and survivin expression.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26707976</pmid><doi>10.1016/j.brainres.2015.12.018</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-8993 |
| ispartof | Brain research, 2016-02, Vol.1632, p.91-97 |
| issn | 0006-8993 1872-6240 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1765980470 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alzheimer׳s disease Amyloid beta-Peptides - toxicity Apoptosis bcl-2-Associated X Protein - biosynthesis Benzodiazepinones - pharmacology Cell Line, Tumor Cell Survival - drug effects Cell Survival - physiology Dose-Response Relationship, Drug Female Gene Expression Regulation Humans Inhibitor of Apoptosis Proteins - biosynthesis Neurology Neuroprotective Agents - pharmacology Peptide Fragments - toxicity Steroidogenesis Steroids Translocator protein (TSPO) |
| title | 4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T03%3A10%3A07IST&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=4%E2%80%B2-Chlorodiazepam%20is%20neuroprotective%20against%20amyloid-beta%20through%20the%20modulation%20of%20survivin%20and%20bax%20protein%20expression%20in%20vitro&rft.jtitle=Brain%20research&rft.au=Arbo,%20B.D&rft.date=2016-02-01&rft.volume=1632&rft.spage=91&rft.epage=97&rft.pages=91-97&rft.issn=0006-8993&rft.eissn=1872-6240&rft_id=info:doi/10.1016/j.brainres.2015.12.018&rft_dat=%3Cproquest_cross%3E1765980470%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=1765980470&rft_id=info:pmid/26707976&rft_els_id=S0006899315009579&rfr_iscdi=true |