Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions
ABSTRACT Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have...
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| Veröffentlicht in: | Journal of applied toxicology 2013-10, Vol.33 (10), p.1180-1186 |
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| creator | Zhang, Xin Xie, Ping Zhang, Xuezhen Zhou, Wenshan Zhao, Sujuan Zhao, Yanyan Cai, Yan |
| description | ABSTRACT
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC‐LR exposure under hypoxic (1% O2) and normoxic (21% O2) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC‐LR in normoxia although decreased in hypoxia. MC‐LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC‐LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c‐IAP2) was significantly up‐regulated by MC‐LR under normoxic condition, suggesting that c‐IAP2 played an important role in the promotion of cell proliferation by MC‐LR. These results indicate that MC‐LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition. Copyright © 2012 John Wiley & Sons, Ltd.
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. |
| doi_str_mv | 10.1002/jat.2749 |
| format | Article |
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Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC‐LR exposure under hypoxic (1% O2) and normoxic (21% O2) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC‐LR in normoxia although decreased in hypoxia. MC‐LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC‐LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c‐IAP2) was significantly up‐regulated by MC‐LR under normoxic condition, suggesting that c‐IAP2 played an important role in the promotion of cell proliferation by MC‐LR. These results indicate that MC‐LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition. Copyright © 2012 John Wiley & Sons, Ltd.
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear.</description><identifier>ISSN: 0260-437X</identifier><identifier>EISSN: 1099-1263</identifier><identifier>DOI: 10.1002/jat.2749</identifier><identifier>PMID: 22539157</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Biotechnology ; Carcinogens - toxicity ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Cell Hypoxia ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Gene expression ; Hep G2 Cells ; Humans ; hypoxia ; Liver - cytology ; Liver - drug effects ; Liver - pathology ; Liver cancer ; MC-LR ; Membrane Potential, Mitochondrial - drug effects ; Microcystins - toxicity ; normoxia ; oxidative stress ; Oxidative Stress - drug effects ; Oxygen - metabolism ; proliferation ; Sod ; Stress concentration ; Stresses ; Superoxide Dismutase - metabolism ; Toxicity ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors ; Viability</subject><ispartof>Journal of applied toxicology, 2013-10, Vol.33 (10), p.1180-1186</ispartof><rights>Copyright © 2012 John Wiley & Sons, Ltd.</rights><rights>Copyright © 2013 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4539-4867810414c885568588e8e5faf19b00cb76d43396e08bb2f2694f1acf0f98753</citedby><cites>FETCH-LOGICAL-c4539-4867810414c885568588e8e5faf19b00cb76d43396e08bb2f2694f1acf0f98753</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%2Fjat.2749$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjat.2749$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22539157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xin</creatorcontrib><creatorcontrib>Xie, Ping</creatorcontrib><creatorcontrib>Zhang, Xuezhen</creatorcontrib><creatorcontrib>Zhou, Wenshan</creatorcontrib><creatorcontrib>Zhao, Sujuan</creatorcontrib><creatorcontrib>Zhao, Yanyan</creatorcontrib><creatorcontrib>Cai, Yan</creatorcontrib><title>Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions</title><title>Journal of applied toxicology</title><addtitle>J. Appl. Toxicol</addtitle><description>ABSTRACT
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC‐LR exposure under hypoxic (1% O2) and normoxic (21% O2) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC‐LR in normoxia although decreased in hypoxia. MC‐LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC‐LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c‐IAP2) was significantly up‐regulated by MC‐LR under normoxic condition, suggesting that c‐IAP2 played an important role in the promotion of cell proliferation by MC‐LR. These results indicate that MC‐LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition. Copyright © 2012 John Wiley & Sons, Ltd.
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biotechnology</subject><subject>Carcinogens - toxicity</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Hypoxia</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Gene expression</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>hypoxia</subject><subject>Liver - cytology</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>MC-LR</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Microcystins - toxicity</subject><subject>normoxia</subject><subject>oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen - metabolism</subject><subject>proliferation</subject><subject>Sod</subject><subject>Stress concentration</subject><subject>Stresses</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Toxicity</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><subject>Viability</subject><issn>0260-437X</issn><issn>1099-1263</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1rFDEcBvAgit22gp9AAl68TM37y7EuurUsWsrWehDCTCahWWeSbTKD3W_f2XatIIinEPLLwz95AHiN0QlGiLxf18MJkUw_AzOMtK4wEfQ5mCEiUMWo_H4ADktZIzSdEfUSHBDCqcZczsCPVboLFjrvnR0KTB72weZkt2UIsVpewhThcOPgmdssCLSu62AXooNjbF2GN9vNw_U6tjCm3D9sbIptGEKK5Ri88HVX3Kv9egSuPn1czc-q5dfF5_npsrJsmqNiSkiFEcPMKsW5UFwppxz3tce6Qcg2UrSMUi0cUk1DPBGaeVxbj7xWktMj8O4xd5PT7ejKYPpQdrPW0aWxGCyk1IxhrP9PGWWIEqXpRN_-RddpzHF6yKSIEpwqpf4ETr9WSnbebHLo67w1GJldOWYqx-zKmeibfeDY9K59gr_bmED1CH6Fzm3_GWTOT1f7wL0PZXB3T77OP42QVHJz_WVhzi8-LL5dz5mh9B7DbaUE</recordid><startdate>201310</startdate><enddate>201310</enddate><creator>Zhang, Xin</creator><creator>Xie, Ping</creator><creator>Zhang, Xuezhen</creator><creator>Zhou, Wenshan</creator><creator>Zhao, Sujuan</creator><creator>Zhao, Yanyan</creator><creator>Cai, Yan</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</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>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>SOI</scope><scope>M7N</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>201310</creationdate><title>Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions</title><author>Zhang, Xin ; Xie, Ping ; Zhang, Xuezhen ; Zhou, Wenshan ; Zhao, Sujuan ; Zhao, Yanyan ; Cai, Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4539-4867810414c885568588e8e5faf19b00cb76d43396e08bb2f2694f1acf0f98753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biotechnology</topic><topic>Carcinogens - toxicity</topic><topic>Caspase 3 - genetics</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Hypoxia</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Gene expression</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>hypoxia</topic><topic>Liver - cytology</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>MC-LR</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Microcystins - toxicity</topic><topic>normoxia</topic><topic>oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxygen - metabolism</topic><topic>proliferation</topic><topic>Sod</topic><topic>Stress concentration</topic><topic>Stresses</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Toxicity</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><topic>Viability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xin</creatorcontrib><creatorcontrib>Xie, Ping</creatorcontrib><creatorcontrib>Zhang, Xuezhen</creatorcontrib><creatorcontrib>Zhou, Wenshan</creatorcontrib><creatorcontrib>Zhao, Sujuan</creatorcontrib><creatorcontrib>Zhao, Yanyan</creatorcontrib><creatorcontrib>Cai, Yan</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>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Environment Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Journal of applied toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xin</au><au>Xie, Ping</au><au>Zhang, Xuezhen</au><au>Zhou, Wenshan</au><au>Zhao, Sujuan</au><au>Zhao, Yanyan</au><au>Cai, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions</atitle><jtitle>Journal of applied toxicology</jtitle><addtitle>J. Appl. Toxicol</addtitle><date>2013-10</date><risdate>2013</risdate><volume>33</volume><issue>10</issue><spage>1180</spage><epage>1186</epage><pages>1180-1186</pages><issn>0260-437X</issn><eissn>1099-1263</eissn><abstract>ABSTRACT
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC‐LR exposure under hypoxic (1% O2) and normoxic (21% O2) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC‐LR in normoxia although decreased in hypoxia. MC‐LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC‐LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c‐IAP2) was significantly up‐regulated by MC‐LR under normoxic condition, suggesting that c‐IAP2 played an important role in the promotion of cell proliferation by MC‐LR. These results indicate that MC‐LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition. Copyright © 2012 John Wiley & Sons, Ltd.
Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>22539157</pmid><doi>10.1002/jat.2749</doi><tpages>7</tpages></addata></record> |
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| subjects | Apoptosis Apoptosis - drug effects bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Biotechnology Carcinogens - toxicity Caspase 3 - genetics Caspase 3 - metabolism Cell Hypoxia Cell Proliferation - drug effects Cell Survival - drug effects Gene expression Hep G2 Cells Humans hypoxia Liver - cytology Liver - drug effects Liver - pathology Liver cancer MC-LR Membrane Potential, Mitochondrial - drug effects Microcystins - toxicity normoxia oxidative stress Oxidative Stress - drug effects Oxygen - metabolism proliferation Sod Stress concentration Stresses Superoxide Dismutase - metabolism Toxicity Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors Viability |
| title | Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions |
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