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Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors
Oxidative shock and production of reactive oxygen species are known to play a major role in situations leading to neuron degeneration, but the precise mechanisms responsible for cell degeneration remain uncertain. In the present article, we have studied in PC 12 cells the effect of cumene hydroxyper...
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| Published in: | Journal of biochemical and molecular toxicology 2011-07, Vol.25 (4), p.205-215 |
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| container_title | Journal of biochemical and molecular toxicology |
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| creator | Vimard, F. Saucet, M. Nicole, O. Feuilloley, M. Duval, D. |
| description | Oxidative shock and production of reactive oxygen species are known to play a major role in situations leading to neuron degeneration, but the precise mechanisms responsible for cell degeneration remain uncertain. In the present article, we have studied in PC 12 cells the effect of cumene hydroxyperoxide on both cell metabolism and morphology. We observed that relatively low concentrations of the drug (100 μM) led to a significant decrease in the cellular content of ATP and reduced glutathione as well as to a decreased mitochondrial potential. These metabolic alterations were followed by an important increase in intracellular free calcium and membrane disruption and death. In parallel, we observed profound changes in cell morphology with a shortening of cell extensions, the formation of ruffles and blebs at the cell surface, and a progressive detachment of the cells from the surface of the culture flasks. We also showed that addition of thiol donors such as N‐acetylcysteine or β‐mercaptoethanol, which were able to enhance cell glutathione content, almost completely protected PC 12 cells from the toxic action of cumene hydroperoxide whereas pretreatment by buthionine sulfoximine, a selective inhibitor of GSH synthesis, enhanced its action. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:205–215, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20377 |
| doi_str_mv | 10.1002/jbt.20377 |
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In the present article, we have studied in PC 12 cells the effect of cumene hydroxyperoxide on both cell metabolism and morphology. We observed that relatively low concentrations of the drug (100 μM) led to a significant decrease in the cellular content of ATP and reduced glutathione as well as to a decreased mitochondrial potential. These metabolic alterations were followed by an important increase in intracellular free calcium and membrane disruption and death. In parallel, we observed profound changes in cell morphology with a shortening of cell extensions, the formation of ruffles and blebs at the cell surface, and a progressive detachment of the cells from the surface of the culture flasks. We also showed that addition of thiol donors such as N‐acetylcysteine or β‐mercaptoethanol, which were able to enhance cell glutathione content, almost completely protected PC 12 cells from the toxic action of cumene hydroperoxide whereas pretreatment by buthionine sulfoximine, a selective inhibitor of GSH synthesis, enhanced its action. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:205–215, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20377</description><identifier>ISSN: 1095-6670</identifier><identifier>EISSN: 1099-0461</identifier><identifier>DOI: 10.1002/jbt.20377</identifier><identifier>PMID: 21812070</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Acetylcysteine ; Acetylcysteine - pharmacology ; Actins - metabolism ; Adenosine Triphosphate - metabolism ; Alkylating Agents - pharmacology ; Alterations of the Cytoskeleton ; Animals ; Antioxidants - pharmacology ; ATP ; Benzene Derivatives - toxicity ; Buthionine sulfoximine ; Buthionine Sulfoximine - pharmacology ; Calcium (intracellular) ; Calcium - metabolism ; Cell culture ; Cell Shape ; Cell Survival - drug effects ; cumene hydroperoxide ; Cytology ; Cytoprotection ; Degeneration ; Dose-Response Relationship, Drug ; Drugs ; Ethylmaleimide - pharmacology ; Evolution of Cytosolic Calcium ; Glutathione ; Glutathione - antagonists & inhibitors ; Glutathione - metabolism ; Glutathione Depletion ; Internet ; Membrane Potential, Mitochondrial ; Mercaptoethanol - pharmacology ; Metabolism ; Mitochondria ; Neurons ; Oxidative Stress - drug effects ; PC12 Cells ; Peroxide Toxicity ; Pheochromocytoma cells ; Protective Effect of N-Acetylcysteine and -Mercaptoethanol ; Rats ; Reactive oxygen species ; Shock ; Thiols ; Toxicity</subject><ispartof>Journal of biochemical and molecular toxicology, 2011-07, Vol.25 (4), p.205-215</ispartof><rights>Copyright © 2011 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4617-6b76433376120e5bbb24069d88967a0b577324e87ae5fe99f767336ca70bb6b93</citedby><cites>FETCH-LOGICAL-c4617-6b76433376120e5bbb24069d88967a0b577324e87ae5fe99f767336ca70bb6b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbt.20377$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbt.20377$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21812070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vimard, F.</creatorcontrib><creatorcontrib>Saucet, M.</creatorcontrib><creatorcontrib>Nicole, O.</creatorcontrib><creatorcontrib>Feuilloley, M.</creatorcontrib><creatorcontrib>Duval, D.</creatorcontrib><title>Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors</title><title>Journal of biochemical and molecular toxicology</title><addtitle>J. Biochem. Mol. Toxicol</addtitle><description>Oxidative shock and production of reactive oxygen species are known to play a major role in situations leading to neuron degeneration, but the precise mechanisms responsible for cell degeneration remain uncertain. In the present article, we have studied in PC 12 cells the effect of cumene hydroxyperoxide on both cell metabolism and morphology. We observed that relatively low concentrations of the drug (100 μM) led to a significant decrease in the cellular content of ATP and reduced glutathione as well as to a decreased mitochondrial potential. These metabolic alterations were followed by an important increase in intracellular free calcium and membrane disruption and death. In parallel, we observed profound changes in cell morphology with a shortening of cell extensions, the formation of ruffles and blebs at the cell surface, and a progressive detachment of the cells from the surface of the culture flasks. We also showed that addition of thiol donors such as N‐acetylcysteine or β‐mercaptoethanol, which were able to enhance cell glutathione content, almost completely protected PC 12 cells from the toxic action of cumene hydroperoxide whereas pretreatment by buthionine sulfoximine, a selective inhibitor of GSH synthesis, enhanced its action. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:205–215, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20377</description><subject>Acetylcysteine</subject><subject>Acetylcysteine - pharmacology</subject><subject>Actins - metabolism</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Alkylating Agents - pharmacology</subject><subject>Alterations of the Cytoskeleton</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>ATP</subject><subject>Benzene Derivatives - toxicity</subject><subject>Buthionine sulfoximine</subject><subject>Buthionine Sulfoximine - pharmacology</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Cell culture</subject><subject>Cell Shape</subject><subject>Cell Survival - drug effects</subject><subject>cumene hydroperoxide</subject><subject>Cytology</subject><subject>Cytoprotection</subject><subject>Degeneration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drugs</subject><subject>Ethylmaleimide - pharmacology</subject><subject>Evolution of Cytosolic Calcium</subject><subject>Glutathione</subject><subject>Glutathione - antagonists & inhibitors</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Depletion</subject><subject>Internet</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Mercaptoethanol - pharmacology</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Neurons</subject><subject>Oxidative Stress - drug effects</subject><subject>PC12 Cells</subject><subject>Peroxide Toxicity</subject><subject>Pheochromocytoma cells</subject><subject>Protective Effect of N-Acetylcysteine and -Mercaptoethanol</subject><subject>Rats</subject><subject>Reactive oxygen species</subject><subject>Shock</subject><subject>Thiols</subject><subject>Toxicity</subject><issn>1095-6670</issn><issn>1099-0461</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9kE1P3DAQhq2qVfloD_wB5FvhEBjHG0_cW9m20BUqHBYh9WLFyUSYZtdbO2k3_75eFrjBaSzNM69eP4wdCDgRAPnpve1PcpCIb9iuAK0zmCjx9uFdZEoh7LC9GO8BoNBYvGc7uShFDgi77Hbu1652_cjdshlqargdeT0saEn8bmyCX1FIRENpz6-nIuc1dV38zK-D76nu3V_iwXfEfcv7O-c73vilD_EDe9dWXaSPj3Of3Xz_Np9eZJdX5z-mXy6zOlXETFlUEyklqtSHCmttPgGlm7LUCiuwBaLMJ1RiRUVLWreoUEpVVwjWKqvlPvu0zV0F_2eg2JuFi5uK1ZL8EE1ZCigLXWIij14lBQjUSRZuQo-3aB18jIFaswpuUYUxQWZj3CTj5sF4Yg8fYwe7oOaZfFKcgNMt8M91NL6cZGZn86fIbHvhYk_r54sq_Dbp91iY25_n5mImZ1P49dXM5H__G5fK</recordid><startdate>201107</startdate><enddate>201107</enddate><creator>Vimard, F.</creator><creator>Saucet, M.</creator><creator>Nicole, O.</creator><creator>Feuilloley, M.</creator><creator>Duval, D.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>201107</creationdate><title>Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors</title><author>Vimard, F. ; Saucet, M. ; Nicole, O. ; Feuilloley, M. ; Duval, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4617-6b76433376120e5bbb24069d88967a0b577324e87ae5fe99f767336ca70bb6b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acetylcysteine</topic><topic>Acetylcysteine - pharmacology</topic><topic>Actins - metabolism</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Alkylating Agents - pharmacology</topic><topic>Alterations of the Cytoskeleton</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>ATP</topic><topic>Benzene Derivatives - toxicity</topic><topic>Buthionine sulfoximine</topic><topic>Buthionine Sulfoximine - pharmacology</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Cell culture</topic><topic>Cell Shape</topic><topic>Cell Survival - drug effects</topic><topic>cumene hydroperoxide</topic><topic>Cytology</topic><topic>Cytoprotection</topic><topic>Degeneration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drugs</topic><topic>Ethylmaleimide - pharmacology</topic><topic>Evolution of Cytosolic Calcium</topic><topic>Glutathione</topic><topic>Glutathione - antagonists & inhibitors</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Depletion</topic><topic>Internet</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Mercaptoethanol - pharmacology</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Neurons</topic><topic>Oxidative Stress - drug effects</topic><topic>PC12 Cells</topic><topic>Peroxide Toxicity</topic><topic>Pheochromocytoma cells</topic><topic>Protective Effect of N-Acetylcysteine and -Mercaptoethanol</topic><topic>Rats</topic><topic>Reactive oxygen species</topic><topic>Shock</topic><topic>Thiols</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vimard, F.</creatorcontrib><creatorcontrib>Saucet, M.</creatorcontrib><creatorcontrib>Nicole, O.</creatorcontrib><creatorcontrib>Feuilloley, M.</creatorcontrib><creatorcontrib>Duval, D.</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Journal of biochemical and molecular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vimard, F.</au><au>Saucet, M.</au><au>Nicole, O.</au><au>Feuilloley, M.</au><au>Duval, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors</atitle><jtitle>Journal of biochemical and molecular toxicology</jtitle><addtitle>J. Biochem. Mol. Toxicol</addtitle><date>2011-07</date><risdate>2011</risdate><volume>25</volume><issue>4</issue><spage>205</spage><epage>215</epage><pages>205-215</pages><issn>1095-6670</issn><eissn>1099-0461</eissn><notes>ArticleID:JBT20377</notes><notes>istex:3FD03076A40AB2E70B27EF69B81A2208BDEA6D9F</notes><notes>ark:/67375/WNG-HJ3JC0ZD-J</notes><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>Oxidative shock and production of reactive oxygen species are known to play a major role in situations leading to neuron degeneration, but the precise mechanisms responsible for cell degeneration remain uncertain. In the present article, we have studied in PC 12 cells the effect of cumene hydroxyperoxide on both cell metabolism and morphology. We observed that relatively low concentrations of the drug (100 μM) led to a significant decrease in the cellular content of ATP and reduced glutathione as well as to a decreased mitochondrial potential. These metabolic alterations were followed by an important increase in intracellular free calcium and membrane disruption and death. In parallel, we observed profound changes in cell morphology with a shortening of cell extensions, the formation of ruffles and blebs at the cell surface, and a progressive detachment of the cells from the surface of the culture flasks. We also showed that addition of thiol donors such as N‐acetylcysteine or β‐mercaptoethanol, which were able to enhance cell glutathione content, almost completely protected PC 12 cells from the toxic action of cumene hydroperoxide whereas pretreatment by buthionine sulfoximine, a selective inhibitor of GSH synthesis, enhanced its action. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:205–215, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20377</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21812070</pmid><doi>10.1002/jbt.20377</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of biochemical and molecular toxicology, 2011-07, Vol.25 (4), p.205-215 |
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| subjects | Acetylcysteine Acetylcysteine - pharmacology Actins - metabolism Adenosine Triphosphate - metabolism Alkylating Agents - pharmacology Alterations of the Cytoskeleton Animals Antioxidants - pharmacology ATP Benzene Derivatives - toxicity Buthionine sulfoximine Buthionine Sulfoximine - pharmacology Calcium (intracellular) Calcium - metabolism Cell culture Cell Shape Cell Survival - drug effects cumene hydroperoxide Cytology Cytoprotection Degeneration Dose-Response Relationship, Drug Drugs Ethylmaleimide - pharmacology Evolution of Cytosolic Calcium Glutathione Glutathione - antagonists & inhibitors Glutathione - metabolism Glutathione Depletion Internet Membrane Potential, Mitochondrial Mercaptoethanol - pharmacology Metabolism Mitochondria Neurons Oxidative Stress - drug effects PC12 Cells Peroxide Toxicity Pheochromocytoma cells Protective Effect of N-Acetylcysteine and -Mercaptoethanol Rats Reactive oxygen species Shock Thiols Toxicity |
| title | Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors |
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