Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes
In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 micr...
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| Veröffentlicht in: | Experimental brain research 2002-03, Vol.143 (2), p.257-263 |
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| creator | JAE RYUN RYU CHAN YOUNG SHIN CHOI, Ji-Woong HYE WON MIN JONG HOON RYU CHOI, Chang-Rak KWANG HO KO |
| description | In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity. |
| doi_str_mv | 10.1007/s00221-001-0991-7 |
| format | Article |
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Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity.</description><identifier>ISSN: 0014-4819</identifier><identifier>EISSN: 1432-1106</identifier><identifier>DOI: 10.1007/s00221-001-0991-7</identifier><identifier>PMID: 11880902</identifier><identifier>CODEN: EXBRAP</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Animals ; Astrocytes - drug effects ; Astrocytes - metabolism ; Biological and medical sciences ; Cell death ; Cell Death - drug effects ; Cells, Cultured ; Fundamental and applied biological sciences. Psychology ; Glioma - metabolism ; Glioma - pathology ; Glutathione - metabolism ; Isolated neuron and nerve. Neuroglia ; Membrane Potentials - drug effects ; Mitochondria - drug effects ; Mitochondria - metabolism ; Prefrontal Cortex - drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; Tumor Cells, Cultured ; Vertebrates: nervous system and sense organs ; Zinc - pharmacology</subject><ispartof>Experimental brain research, 2002-03, Vol.143 (2), p.257-263</ispartof><rights>2002 INIST-CNRS</rights><rights>Springer-Verlag 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-2919ae546519eac1d77a196c1cbc38c0865ba05057559388ab28c784807e98bd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13527853$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11880902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JAE RYUN RYU</creatorcontrib><creatorcontrib>CHAN YOUNG SHIN</creatorcontrib><creatorcontrib>CHOI, Ji-Woong</creatorcontrib><creatorcontrib>HYE WON MIN</creatorcontrib><creatorcontrib>JONG HOON RYU</creatorcontrib><creatorcontrib>CHOI, Chang-Rak</creatorcontrib><creatorcontrib>KWANG HO KO</creatorcontrib><title>Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes</title><title>Experimental brain research</title><addtitle>Exp Brain Res</addtitle><description>In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity.</description><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cells, Cultured</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Glutathione - metabolism</subject><subject>Isolated neuron and nerve. Neuroglia</subject><subject>Membrane Potentials - drug effects</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species</subject><subject>Tumor Cells, Cultured</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Zinc - pharmacology</subject><issn>0014-4819</issn><issn>1432-1106</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkE1LxDAQhoMouq7-AC8SBL1VM0nTJEfxGwQveg7TNKuVbrsm6UF_vSlbEDwMYZjnHSYPISfALoExdRUZ4xwKxnIZA4XaIQsoBS8AWLVLFnlQFqUGc0AOY_ycWqHYPjkA0JoZxhcEb_2m86kdejqsaNungM533dhhoO_dmDB95Jmna9-0mHykP23virZvRucbOqG08RnKURow0U1o1xi-KcYUBvedE0dkb4Vd9MfzuyRv93evN4_F88vD0831c-FKCangBgx6WVYSjEcHjVIIpnLgaie0Y7qSNTLJpJLSCK2x5topXWqmvNF1I5bkYrt3E4av0cdk122cDsTeD2O0oEVVacUzePYP_BzG0OfbLAcJQoBWGYIt5MIQY_ArO__MArOTfLuVb7NUO8m3U-Z0XjzW2ddfYradgfMZwOiwWwXsXRv_OCG50lKIXzz_jEA</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>JAE RYUN RYU</creator><creator>CHAN YOUNG SHIN</creator><creator>CHOI, Ji-Woong</creator><creator>HYE WON MIN</creator><creator>JONG HOON RYU</creator><creator>CHOI, Chang-Rak</creator><creator>KWANG HO KO</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>0-V</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88J</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2R</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>POGQB</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PRQQA</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20020301</creationdate><title>Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes</title><author>JAE RYUN RYU ; CHAN YOUNG SHIN ; CHOI, Ji-Woong ; HYE WON MIN ; JONG HOON RYU ; CHOI, Chang-Rak ; KWANG HO KO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-2919ae546519eac1d77a196c1cbc38c0865ba05057559388ab28c784807e98bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell death</topic><topic>Cell Death - drug effects</topic><topic>Cells, Cultured</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Glutathione - metabolism</topic><topic>Isolated neuron and nerve. Neuroglia</topic><topic>Membrane Potentials - drug effects</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species</topic><topic>Tumor Cells, Cultured</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Zinc - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JAE RYUN RYU</creatorcontrib><creatorcontrib>CHAN YOUNG SHIN</creatorcontrib><creatorcontrib>CHOI, Ji-Woong</creatorcontrib><creatorcontrib>HYE WON MIN</creatorcontrib><creatorcontrib>JONG HOON RYU</creatorcontrib><creatorcontrib>CHOI, Chang-Rak</creatorcontrib><creatorcontrib>KWANG HO KO</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Social Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Social Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest Sociology & Social Sciences Collection</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Social Sciences</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Experimental brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JAE RYUN RYU</au><au>CHAN YOUNG SHIN</au><au>CHOI, Ji-Woong</au><au>HYE WON MIN</au><au>JONG HOON RYU</au><au>CHOI, Chang-Rak</au><au>KWANG HO KO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes</atitle><jtitle>Experimental brain research</jtitle><addtitle>Exp Brain Res</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>143</volume><issue>2</issue><spage>257</spage><epage>263</epage><pages>257-263</pages><issn>0014-4819</issn><eissn>1432-1106</eissn><coden>EXBRAP</coden><abstract>In the present study, we investigated the possible mechanisms of cellular injury induced by zinc in rat primary astrocytes and C6 glioma cells. Reactive oxygen species (ROS) production, cellular glutathione (GSH) level and mitochondrial transmembrane potential were examined. Exposure to 200-300 microM Zn2+ for 24 h resulted in significant lactate dehydrogenase (LDH) release in rat primary astrocytes and C6 glioma cells. An exposure of 200 microM Zn2+ resulted in profound morphological changes, for example, shrunken and fragmented nuclei. Pretreatment of a protein synthesis inhibitor, cycloheximide, did not attenuate cellular toxicity induced by Zn2+. Zn2+ exposure increased intracellular ROS levels by about 250%, and depleted cellular GSH within 2 h, which preceded observable LDH release from the cell. Addition of GSH, N-acetylcysteine (NAC) and ascorbic acid substantially attenuated cellular death induced by Zn+ in a concentration dependent manner. ROS production and morphological changes induced by zinc were also inhibited by co-treatment of GSH or NAC with Zn2+. Zn2+ significantly depolarized mitochondrial transmembrane potential, which was reversed by co-treatment of GSH or NAC with zinc. In summary, ROS generation, GSH depletion and mitochondrial dysfunction may be key factors in Zn2+-induced glial toxicity.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>11880902</pmid><doi>10.1007/s00221-001-0991-7</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Astrocytes - drug effects Astrocytes - metabolism Biological and medical sciences Cell death Cell Death - drug effects Cells, Cultured Fundamental and applied biological sciences. Psychology Glioma - metabolism Glioma - pathology Glutathione - metabolism Isolated neuron and nerve. Neuroglia Membrane Potentials - drug effects Mitochondria - drug effects Mitochondria - metabolism Prefrontal Cortex - drug effects Rats Rats, Sprague-Dawley Reactive Oxygen Species Tumor Cells, Cultured Vertebrates: nervous system and sense organs Zinc - pharmacology |
| title | Depletion of intracellular glutathione mediates zinc-induced cell death in rat primary astrocytes |
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