The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis
3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the pres...
Gespeichert in:
| Veröffentlicht in: | Biochemical and biophysical research communications 2001-06, Vol.284 (2), p.261-267 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 267 |
|---|---|
| container_issue | 2 |
| container_start_page | 261 |
| container_title | Biochemical and biophysical research communications |
| container_volume | 284 |
| creator | Lee, Myoung-Woo Park, Soon Cheol Chae, Hee-Sun Bach, Jae-Hyung Lee, Hyun-Jung Lee, Sang Hyung Kang, Yong Koo Kim, Kyung Yong Lee, Won Bok Kim, Sung Su |
| description | 3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis. |
| doi_str_mv | 10.1006/bbrc.2001.4938 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17893766</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006291X01949381</els_id><sourcerecordid>17893766</sourcerecordid><originalsourceid>FETCH-LOGICAL-c286t-7f5620ee87a6b96b202c4216b946ced60dfe0516b4e4d4ac2caeec5ff1c275be3</originalsourceid><addsrcrecordid>eNp1kMFLwzAUh4Mobk6vHqUnb61JmqbtcQx1g6HDTfAW0vRVo10zk3bY_96UDTx5eu_B93689yF0TXBEMOZ3RWFVRDEmEcvj7ASNCc5xSAlmp2iMPRHSnLyN0IVzn54ijOfnaERInLMsJWO03nxAsLKmBdXqPQQvpobAVMF8vcpxIN-lblwbxOG8L6356b_6prPQ6AbCRVN2CsrgCTprGlkH053ZtcZpd4nOKlk7uDrWCXp9uN_M5uHy-XExmy5DRTPehmmVcIoBslTyIucFxVQxSnzPuA_muKwAJ35mwEomFVUSQCVVRRRNkwLiCbo95O6s-e7AtWKrnYK6lg2YzgmSZnmccu7B6AAqa5yzUImd1Vtpe0GwGDSKQaMYNIpBo1-4OSZ3xRbKP_zozQPZAQD_316DFU5paPzZ2nqTojT6v-xfRvCB9g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17893766</pqid></control><display><type>article</type><title>The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Lee, Myoung-Woo ; Park, Soon Cheol ; Chae, Hee-Sun ; Bach, Jae-Hyung ; Lee, Hyun-Jung ; Lee, Sang Hyung ; Kang, Yong Koo ; Kim, Kyung Yong ; Lee, Won Bok ; Kim, Sung Su</creator><creatorcontrib>Lee, Myoung-Woo ; Park, Soon Cheol ; Chae, Hee-Sun ; Bach, Jae-Hyung ; Lee, Hyun-Jung ; Lee, Sang Hyung ; Kang, Yong Koo ; Kim, Kyung Yong ; Lee, Won Bok ; Kim, Sung Su</creatorcontrib><description>3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2001.4938</identifier><identifier>PMID: 11394871</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3-hydroxykynurenine ; apoptosis ; Apoptosis - drug effects ; Bisbenzimidazole ; Blotting, Western ; caspase ; Caspases - metabolism ; Cell Line ; Cell Survival - drug effects ; Cytoprotection - drug effects ; Dose-Response Relationship, Drug ; Enzyme Activation - drug effects ; heat shock protein 90 ; Heat-Shock Proteins ; Heat-Shock Response ; HSP27 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins - genetics ; HSP70 Heat-Shock Proteins - metabolism ; HSP90 Heat-Shock Proteins - genetics ; HSP90 Heat-Shock Proteins - metabolism ; HSP90 Heat-Shock Proteins - pharmacology ; Humans ; Kynurenine - analogs & derivatives ; Kynurenine - antagonists & inhibitors ; Kynurenine - toxicity ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Oligonucleotides, Antisense - pharmacology ; RNA, Messenger - antagonists & inhibitors ; RNA, Messenger - metabolism ; Temperature</subject><ispartof>Biochemical and biophysical research communications, 2001-06, Vol.284 (2), p.261-267</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c286t-7f5620ee87a6b96b202c4216b946ced60dfe0516b4e4d4ac2caeec5ff1c275be3</citedby><cites>FETCH-LOGICAL-c286t-7f5620ee87a6b96b202c4216b946ced60dfe0516b4e4d4ac2caeec5ff1c275be3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.2001.4938$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11394871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Myoung-Woo</creatorcontrib><creatorcontrib>Park, Soon Cheol</creatorcontrib><creatorcontrib>Chae, Hee-Sun</creatorcontrib><creatorcontrib>Bach, Jae-Hyung</creatorcontrib><creatorcontrib>Lee, Hyun-Jung</creatorcontrib><creatorcontrib>Lee, Sang Hyung</creatorcontrib><creatorcontrib>Kang, Yong Koo</creatorcontrib><creatorcontrib>Kim, Kyung Yong</creatorcontrib><creatorcontrib>Lee, Won Bok</creatorcontrib><creatorcontrib>Kim, Sung Su</creatorcontrib><title>The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis.</description><subject>3-hydroxykynurenine</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bisbenzimidazole</subject><subject>Blotting, Western</subject><subject>caspase</subject><subject>Caspases - metabolism</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Cytoprotection - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation - drug effects</subject><subject>heat shock protein 90</subject><subject>Heat-Shock Proteins</subject><subject>Heat-Shock Response</subject><subject>HSP27 Heat-Shock Proteins</subject><subject>HSP70 Heat-Shock Proteins - genetics</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>HSP90 Heat-Shock Proteins - genetics</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>HSP90 Heat-Shock Proteins - pharmacology</subject><subject>Humans</subject><subject>Kynurenine - analogs & derivatives</subject><subject>Kynurenine - antagonists & inhibitors</subject><subject>Kynurenine - toxicity</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuroblastoma - pathology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>RNA, Messenger - antagonists & inhibitors</subject><subject>RNA, Messenger - metabolism</subject><subject>Temperature</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFLwzAUh4Mobk6vHqUnb61JmqbtcQx1g6HDTfAW0vRVo10zk3bY_96UDTx5eu_B93689yF0TXBEMOZ3RWFVRDEmEcvj7ASNCc5xSAlmp2iMPRHSnLyN0IVzn54ijOfnaERInLMsJWO03nxAsLKmBdXqPQQvpobAVMF8vcpxIN-lblwbxOG8L6356b_6prPQ6AbCRVN2CsrgCTprGlkH053ZtcZpd4nOKlk7uDrWCXp9uN_M5uHy-XExmy5DRTPehmmVcIoBslTyIucFxVQxSnzPuA_muKwAJ35mwEomFVUSQCVVRRRNkwLiCbo95O6s-e7AtWKrnYK6lg2YzgmSZnmccu7B6AAqa5yzUImd1Vtpe0GwGDSKQaMYNIpBo1-4OSZ3xRbKP_zozQPZAQD_316DFU5paPzZ2nqTojT6v-xfRvCB9g</recordid><startdate>20010608</startdate><enddate>20010608</enddate><creator>Lee, Myoung-Woo</creator><creator>Park, Soon Cheol</creator><creator>Chae, Hee-Sun</creator><creator>Bach, Jae-Hyung</creator><creator>Lee, Hyun-Jung</creator><creator>Lee, Sang Hyung</creator><creator>Kang, Yong Koo</creator><creator>Kim, Kyung Yong</creator><creator>Lee, Won Bok</creator><creator>Kim, Sung Su</creator><general>Elsevier Inc</general><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>7TM</scope></search><sort><creationdate>20010608</creationdate><title>The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis</title><author>Lee, Myoung-Woo ; Park, Soon Cheol ; Chae, Hee-Sun ; Bach, Jae-Hyung ; Lee, Hyun-Jung ; Lee, Sang Hyung ; Kang, Yong Koo ; Kim, Kyung Yong ; Lee, Won Bok ; Kim, Sung Su</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-7f5620ee87a6b96b202c4216b946ced60dfe0516b4e4d4ac2caeec5ff1c275be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>3-hydroxykynurenine</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bisbenzimidazole</topic><topic>Blotting, Western</topic><topic>caspase</topic><topic>Caspases - metabolism</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Cytoprotection - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation - drug effects</topic><topic>heat shock protein 90</topic><topic>Heat-Shock Proteins</topic><topic>Heat-Shock Response</topic><topic>HSP27 Heat-Shock Proteins</topic><topic>HSP70 Heat-Shock Proteins - genetics</topic><topic>HSP70 Heat-Shock Proteins - metabolism</topic><topic>HSP90 Heat-Shock Proteins - genetics</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>HSP90 Heat-Shock Proteins - pharmacology</topic><topic>Humans</topic><topic>Kynurenine - analogs & derivatives</topic><topic>Kynurenine - antagonists & inhibitors</topic><topic>Kynurenine - toxicity</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuroblastoma - pathology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>RNA, Messenger - antagonists & inhibitors</topic><topic>RNA, Messenger - metabolism</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Myoung-Woo</creatorcontrib><creatorcontrib>Park, Soon Cheol</creatorcontrib><creatorcontrib>Chae, Hee-Sun</creatorcontrib><creatorcontrib>Bach, Jae-Hyung</creatorcontrib><creatorcontrib>Lee, Hyun-Jung</creatorcontrib><creatorcontrib>Lee, Sang Hyung</creatorcontrib><creatorcontrib>Kang, Yong Koo</creatorcontrib><creatorcontrib>Kim, Kyung Yong</creatorcontrib><creatorcontrib>Lee, Won Bok</creatorcontrib><creatorcontrib>Kim, Sung Su</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Myoung-Woo</au><au>Park, Soon Cheol</au><au>Chae, Hee-Sun</au><au>Bach, Jae-Hyung</au><au>Lee, Hyun-Jung</au><au>Lee, Sang Hyung</au><au>Kang, Yong Koo</au><au>Kim, Kyung Yong</au><au>Lee, Won Bok</au><au>Kim, Sung Su</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-06-08</date><risdate>2001</risdate><volume>284</volume><issue>2</issue><spage>261</spage><epage>267</epage><pages>261-267</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11394871</pmid><doi>10.1006/bbrc.2001.4938</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-291X |
| ispartof | Biochemical and biophysical research communications, 2001-06, Vol.284 (2), p.261-267 |
| issn | 0006-291X 1090-2104 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17893766 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 3-hydroxykynurenine apoptosis Apoptosis - drug effects Bisbenzimidazole Blotting, Western caspase Caspases - metabolism Cell Line Cell Survival - drug effects Cytoprotection - drug effects Dose-Response Relationship, Drug Enzyme Activation - drug effects heat shock protein 90 Heat-Shock Proteins Heat-Shock Response HSP27 Heat-Shock Proteins HSP70 Heat-Shock Proteins - genetics HSP70 Heat-Shock Proteins - metabolism HSP90 Heat-Shock Proteins - genetics HSP90 Heat-Shock Proteins - metabolism HSP90 Heat-Shock Proteins - pharmacology Humans Kynurenine - analogs & derivatives Kynurenine - antagonists & inhibitors Kynurenine - toxicity Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neuroblastoma - metabolism Neuroblastoma - pathology Neurons - cytology Neurons - drug effects Neurons - metabolism Oligonucleotides, Antisense - pharmacology RNA, Messenger - antagonists & inhibitors RNA, Messenger - metabolism Temperature |
| title | The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T16%3A06%3A39IST&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=The%20Protective%20Role%20of%20HSP90%20against%203-Hydroxykynurenine-Induced%20Neuronal%20Apoptosis&rft.jtitle=Biochemical%20and%20biophysical%20research%20communications&rft.au=Lee,%20Myoung-Woo&rft.date=2001-06-08&rft.volume=284&rft.issue=2&rft.spage=261&rft.epage=267&rft.pages=261-267&rft.issn=0006-291X&rft.eissn=1090-2104&rft_id=info:doi/10.1006/bbrc.2001.4938&rft_dat=%3Cproquest_cross%3E17893766%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=17893766&rft_id=info:pmid/11394871&rft_els_id=S0006291X01949381&rfr_iscdi=true |