Role of autophagy in arsenite-induced neurotoxicity: The involvement of α-synuclein
•Our study first shows arsenite-induced autophagy in primary cortical neurons.•Atg7 siRNA transfection ameliorates arsenite-induced autophagy and neurotoxicity.•Autophagy plays a pro-death role in arsenite-induced neurotoxicity.•Arsenite-induced decreases in α-synuclein (17kDa) may be due to autopha...
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| Veröffentlicht in: | Toxicology letters 2015-03, Vol.233 (3), p.239-245 |
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| creator | Teng, Yu-Chun Jeng, Chung Jiuan Huang, Hui-Ju Lin, Anya Maan-Yuh |
| description | •Our study first shows arsenite-induced autophagy in primary cortical neurons.•Atg7 siRNA transfection ameliorates arsenite-induced autophagy and neurotoxicity.•Autophagy plays a pro-death role in arsenite-induced neurotoxicity.•Arsenite-induced decreases in α-synuclein (17kDa) may be due to autophagy.•Arsenics differentially induce autophagy and neurotoxicity.
In the present study, the role of autophagy in sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation with arsenite concentration-dependently increased LC3-II levels (a biomarker of autophagy), indicating that arsenite is capable of inducing autophagy. Co-localization of fluorescent puncta of monodansylcadaverine (a fluorescent dye of autophagic vacuoles) and LysoTracker Red (a fluorescent dye of lysosomes) as well as chloroquine-induced enhancement of arsenite-elevated LC3-II levels suggest that arsenite induced autolysosome formation in primary cultured cortical neurons. Incubation of 3-methyladenine (an autophagy inhibitor) prevented arsenite-induced LC3-II elevation, autolysosome formation, reduction in GAP 43 (a biomarker of neurite outgrowth), caspase 3 activation and neuronal cell loss. Furthermore, Atg7 siRNA transfection attenuated arsenite-induced autophagy and neurotoxicity. At the same time, Atg7siRNA transfection ameliorated arsenite-induced reduction in α-synuclein levels (a synaptic protein essential for neuroplasticity), suggesting that arsenite via autophagy may engulf α-synuclein. Cytotoxic activities as well as potencies in elevating LC3-II and reducing α-synuclein levels by arsenite, arsenate, monomethyl arsenite (MMAIII), and dimethyl arsenate (DMAV) were compared as follows: MMAIII>arsenite»arsenate and DMAV. Taken together, autophagy appears to play a pro-death role in arsenics-induced neurotoxicity. Moreover, autophagy and subsequent reduction in α-synuclein levels may be a vicious cycle in arsenics-induced neurotoxicity. |
| doi_str_mv | 10.1016/j.toxlet.2015.01.018 |
| format | Article |
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In the present study, the role of autophagy in sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation with arsenite concentration-dependently increased LC3-II levels (a biomarker of autophagy), indicating that arsenite is capable of inducing autophagy. Co-localization of fluorescent puncta of monodansylcadaverine (a fluorescent dye of autophagic vacuoles) and LysoTracker Red (a fluorescent dye of lysosomes) as well as chloroquine-induced enhancement of arsenite-elevated LC3-II levels suggest that arsenite induced autolysosome formation in primary cultured cortical neurons. Incubation of 3-methyladenine (an autophagy inhibitor) prevented arsenite-induced LC3-II elevation, autolysosome formation, reduction in GAP 43 (a biomarker of neurite outgrowth), caspase 3 activation and neuronal cell loss. Furthermore, Atg7 siRNA transfection attenuated arsenite-induced autophagy and neurotoxicity. At the same time, Atg7siRNA transfection ameliorated arsenite-induced reduction in α-synuclein levels (a synaptic protein essential for neuroplasticity), suggesting that arsenite via autophagy may engulf α-synuclein. Cytotoxic activities as well as potencies in elevating LC3-II and reducing α-synuclein levels by arsenite, arsenate, monomethyl arsenite (MMAIII), and dimethyl arsenate (DMAV) were compared as follows: MMAIII>arsenite»arsenate and DMAV. Taken together, autophagy appears to play a pro-death role in arsenics-induced neurotoxicity. Moreover, autophagy and subsequent reduction in α-synuclein levels may be a vicious cycle in arsenics-induced neurotoxicity.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/j.toxlet.2015.01.018</identifier><identifier>PMID: 25639566</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>alpha-Synuclein - analysis ; alpha-Synuclein - physiology ; Animals ; Arsenates ; Arsenic ; Arsenite ; Arsenites - toxicity ; Atg7siRNA transfection ; Autolysosome ; Autophagy ; Autophagy - drug effects ; Autophagy - physiology ; Autophagy-Related Protein 7 ; Biomarkers ; Dyes ; Female ; Fluorescence ; Formations ; Microtubule-Associated Proteins - analysis ; Neurons ; Neurotoxicity ; Neurotoxicity Syndromes - etiology ; Rats ; Rats, Sprague-Dawley ; Reduction ; Ubiquitin-Activating Enzymes - physiology ; α-Synuclein</subject><ispartof>Toxicology letters, 2015-03, Vol.233 (3), p.239-245</ispartof><rights>2015 Elsevier Ireland Ltd</rights><rights>Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-f005ec16e04ee1d5defda36ea8ea03585f2458ae90b89bb87a6ece8b03c1c3743</citedby><cites>FETCH-LOGICAL-c428t-f005ec16e04ee1d5defda36ea8ea03585f2458ae90b89bb87a6ece8b03c1c3743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378427415000302$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25639566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teng, Yu-Chun</creatorcontrib><creatorcontrib>Jeng, Chung Jiuan</creatorcontrib><creatorcontrib>Huang, Hui-Ju</creatorcontrib><creatorcontrib>Lin, Anya Maan-Yuh</creatorcontrib><title>Role of autophagy in arsenite-induced neurotoxicity: The involvement of α-synuclein</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>•Our study first shows arsenite-induced autophagy in primary cortical neurons.•Atg7 siRNA transfection ameliorates arsenite-induced autophagy and neurotoxicity.•Autophagy plays a pro-death role in arsenite-induced neurotoxicity.•Arsenite-induced decreases in α-synuclein (17kDa) may be due to autophagy.•Arsenics differentially induce autophagy and neurotoxicity.
In the present study, the role of autophagy in sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation with arsenite concentration-dependently increased LC3-II levels (a biomarker of autophagy), indicating that arsenite is capable of inducing autophagy. Co-localization of fluorescent puncta of monodansylcadaverine (a fluorescent dye of autophagic vacuoles) and LysoTracker Red (a fluorescent dye of lysosomes) as well as chloroquine-induced enhancement of arsenite-elevated LC3-II levels suggest that arsenite induced autolysosome formation in primary cultured cortical neurons. Incubation of 3-methyladenine (an autophagy inhibitor) prevented arsenite-induced LC3-II elevation, autolysosome formation, reduction in GAP 43 (a biomarker of neurite outgrowth), caspase 3 activation and neuronal cell loss. Furthermore, Atg7 siRNA transfection attenuated arsenite-induced autophagy and neurotoxicity. At the same time, Atg7siRNA transfection ameliorated arsenite-induced reduction in α-synuclein levels (a synaptic protein essential for neuroplasticity), suggesting that arsenite via autophagy may engulf α-synuclein. Cytotoxic activities as well as potencies in elevating LC3-II and reducing α-synuclein levels by arsenite, arsenate, monomethyl arsenite (MMAIII), and dimethyl arsenate (DMAV) were compared as follows: MMAIII>arsenite»arsenate and DMAV. Taken together, autophagy appears to play a pro-death role in arsenics-induced neurotoxicity. Moreover, autophagy and subsequent reduction in α-synuclein levels may be a vicious cycle in arsenics-induced neurotoxicity.</description><subject>alpha-Synuclein - analysis</subject><subject>alpha-Synuclein - physiology</subject><subject>Animals</subject><subject>Arsenates</subject><subject>Arsenic</subject><subject>Arsenite</subject><subject>Arsenites - toxicity</subject><subject>Atg7siRNA transfection</subject><subject>Autolysosome</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Autophagy - physiology</subject><subject>Autophagy-Related Protein 7</subject><subject>Biomarkers</subject><subject>Dyes</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Formations</subject><subject>Microtubule-Associated Proteins - analysis</subject><subject>Neurons</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reduction</subject><subject>Ubiquitin-Activating Enzymes - physiology</subject><subject>α-Synuclein</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtqHDEQRUWwiSdO_sCYXnrTk1Kr9egsDMbkBQZDmKyFWl0da-iRJpJ68HyWf8TfFA3jZBkMBbU5ty51CLmgsKRAxcf1MofHCfOyAcqXQMuoN2RBlexqRkV3QhbApKrbRrZn5F1KawAQreBvyVnDBeu4EAuy-hEmrMJYmTmH7YP5ta-cr0xM6F3G2vlhtjhUHucYSp-zLu8_VasHLNguTDvcoM-H_PNTnfZ-thM6_56cjmZK-OFln5OfXz6vbr_Vd_dfv9_e3NW2bVSuRwCOlgqEFpEOfMBxMEygUWiAccXHpuXKYAe96vpeSSPQouqBWWqZbNk5uTre3cbwe8aU9cYli9NkPIY5aSolsPJ_070CbaSQUgpa0PaI2hhSijjqbXQbE_eagj6o12t9VK8P6jXQMqrELl8a5n6Dw7_QX9cFuD4CWJTsHEadrENf9LqINushuP83_AEuJ5kX</recordid><startdate>20150318</startdate><enddate>20150318</enddate><creator>Teng, Yu-Chun</creator><creator>Jeng, Chung Jiuan</creator><creator>Huang, Hui-Ju</creator><creator>Lin, Anya Maan-Yuh</creator><general>Elsevier Ireland Ltd</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>7U7</scope><scope>C1K</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>20150318</creationdate><title>Role of autophagy in arsenite-induced neurotoxicity: The involvement of α-synuclein</title><author>Teng, Yu-Chun ; Jeng, Chung Jiuan ; Huang, Hui-Ju ; Lin, Anya Maan-Yuh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-f005ec16e04ee1d5defda36ea8ea03585f2458ae90b89bb87a6ece8b03c1c3743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>alpha-Synuclein - analysis</topic><topic>alpha-Synuclein - physiology</topic><topic>Animals</topic><topic>Arsenates</topic><topic>Arsenic</topic><topic>Arsenite</topic><topic>Arsenites - toxicity</topic><topic>Atg7siRNA transfection</topic><topic>Autolysosome</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Autophagy - physiology</topic><topic>Autophagy-Related Protein 7</topic><topic>Biomarkers</topic><topic>Dyes</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Formations</topic><topic>Microtubule-Associated Proteins - analysis</topic><topic>Neurons</topic><topic>Neurotoxicity</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reduction</topic><topic>Ubiquitin-Activating Enzymes - physiology</topic><topic>α-Synuclein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teng, Yu-Chun</creatorcontrib><creatorcontrib>Jeng, Chung Jiuan</creatorcontrib><creatorcontrib>Huang, Hui-Ju</creatorcontrib><creatorcontrib>Lin, Anya Maan-Yuh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teng, Yu-Chun</au><au>Jeng, Chung Jiuan</au><au>Huang, Hui-Ju</au><au>Lin, Anya Maan-Yuh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of autophagy in arsenite-induced neurotoxicity: The involvement of α-synuclein</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>2015-03-18</date><risdate>2015</risdate><volume>233</volume><issue>3</issue><spage>239</spage><epage>245</epage><pages>239-245</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><abstract>•Our study first shows arsenite-induced autophagy in primary cortical neurons.•Atg7 siRNA transfection ameliorates arsenite-induced autophagy and neurotoxicity.•Autophagy plays a pro-death role in arsenite-induced neurotoxicity.•Arsenite-induced decreases in α-synuclein (17kDa) may be due to autophagy.•Arsenics differentially induce autophagy and neurotoxicity.
In the present study, the role of autophagy in sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation with arsenite concentration-dependently increased LC3-II levels (a biomarker of autophagy), indicating that arsenite is capable of inducing autophagy. Co-localization of fluorescent puncta of monodansylcadaverine (a fluorescent dye of autophagic vacuoles) and LysoTracker Red (a fluorescent dye of lysosomes) as well as chloroquine-induced enhancement of arsenite-elevated LC3-II levels suggest that arsenite induced autolysosome formation in primary cultured cortical neurons. Incubation of 3-methyladenine (an autophagy inhibitor) prevented arsenite-induced LC3-II elevation, autolysosome formation, reduction in GAP 43 (a biomarker of neurite outgrowth), caspase 3 activation and neuronal cell loss. Furthermore, Atg7 siRNA transfection attenuated arsenite-induced autophagy and neurotoxicity. At the same time, Atg7siRNA transfection ameliorated arsenite-induced reduction in α-synuclein levels (a synaptic protein essential for neuroplasticity), suggesting that arsenite via autophagy may engulf α-synuclein. Cytotoxic activities as well as potencies in elevating LC3-II and reducing α-synuclein levels by arsenite, arsenate, monomethyl arsenite (MMAIII), and dimethyl arsenate (DMAV) were compared as follows: MMAIII>arsenite»arsenate and DMAV. Taken together, autophagy appears to play a pro-death role in arsenics-induced neurotoxicity. Moreover, autophagy and subsequent reduction in α-synuclein levels may be a vicious cycle in arsenics-induced neurotoxicity.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>25639566</pmid><doi>10.1016/j.toxlet.2015.01.018</doi><tpages>7</tpages></addata></record> |
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| subjects | alpha-Synuclein - analysis alpha-Synuclein - physiology Animals Arsenates Arsenic Arsenite Arsenites - toxicity Atg7siRNA transfection Autolysosome Autophagy Autophagy - drug effects Autophagy - physiology Autophagy-Related Protein 7 Biomarkers Dyes Female Fluorescence Formations Microtubule-Associated Proteins - analysis Neurons Neurotoxicity Neurotoxicity Syndromes - etiology Rats Rats, Sprague-Dawley Reduction Ubiquitin-Activating Enzymes - physiology α-Synuclein |
| title | Role of autophagy in arsenite-induced neurotoxicity: The involvement of α-synuclein |
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