Hepatitis C Virus Nonstructural Protein 5A Inhibits Tumor Necrosis Factor–α–Mediated Apoptosis in Huh7 Cells
To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)–α. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-...
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| Veröffentlicht in: | The Journal of infectious diseases 2003-11, Vol.188 (10), p.1537-1544 |
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| container_title | The Journal of infectious diseases |
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| creator | Miyasaka, Yuka Enomoto, Nobuyuki Kurosaki, Masayuki Sakamoto, Naoya Kanazawa, Nobuhiko Kohashi, Takahiro Ueda, Eri Maekawa, Shinya Watanabe, Hideki Izumi, Namiki Sato, Chifumi Watanabe, Mamoru |
| description | To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)–α. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-α treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to |
| doi_str_mv | 10.1086/379253 |
| format | Article |
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The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-α treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to <50% in Huh7-NS5A compared with control cells. Nuclear factor–κB activation was the same in both cell types, whereas caspase-8, -9, and -3 activity was decreased in Huh7-NS5A cells, compared with control cells, which indicates that the inhibition of caspase-8 activation is responsible for the antiapoptotic effect of the NS5A protein. The coexpression of NS5A did not inhibit apoptosis induced by caspase-8 or Fas-associating death domain protein expression. These findings suggest that the NS5A protein inhibits the apoptotic effect of TNF-α upstream of caspase-8 in the apoptosis cascade</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/379253</identifier><identifier>PMID: 14624380</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Apoptosis ; Apoptosis - physiology ; Arabidopsis Proteins - physiology ; Biological and medical sciences ; Caspase 8 ; Caspase 9 ; Caspases - physiology ; Cell Line ; Chronic hepatitis ; Dactinomycin - pharmacology ; Fatty Acid Desaturases - physiology ; Fundamental and applied biological sciences. Psychology ; Hepacivirus ; Hepacivirus - genetics ; Hepacivirus - metabolism ; Hepatitis C ; Hepatitis C - pathology ; Hepatitis C virus ; Hepatocytes ; Hepatocytes - cytology ; Humans ; Infections ; Infectious diseases ; Medical sciences ; Microbiology ; Miscellaneous ; NF-kappa B - physiology ; NS5A protein ; Nucleic Acid Synthesis Inhibitors - pharmacology ; Oligoribonucleotides, Antisense - genetics ; Oligoribonucleotides, Antisense - pharmacology ; Signal Transduction - immunology ; T lymphocytes ; Transfection ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - physiology ; Tumor necrosis factors ; Viability ; Viral Nonstructural Proteins - genetics ; Viral Nonstructural Proteins - physiology ; Virology ; Viruses</subject><ispartof>The Journal of infectious diseases, 2003-11, Vol.188 (10), p.1537-1544</ispartof><rights>Copyright 2003 Infectious Diseases Society of America</rights><rights>2003 by the Infectious Diseases Society of America 2003</rights><rights>2004 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Nov 15 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-8fcdd95e2d90e1b44b81679e6d49282e05004a37ccb0ee2d0c9e017003ef402f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30075760$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30075760$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15353156$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14624380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyasaka, Yuka</creatorcontrib><creatorcontrib>Enomoto, Nobuyuki</creatorcontrib><creatorcontrib>Kurosaki, Masayuki</creatorcontrib><creatorcontrib>Sakamoto, Naoya</creatorcontrib><creatorcontrib>Kanazawa, Nobuhiko</creatorcontrib><creatorcontrib>Kohashi, Takahiro</creatorcontrib><creatorcontrib>Ueda, Eri</creatorcontrib><creatorcontrib>Maekawa, Shinya</creatorcontrib><creatorcontrib>Watanabe, Hideki</creatorcontrib><creatorcontrib>Izumi, Namiki</creatorcontrib><creatorcontrib>Sato, Chifumi</creatorcontrib><creatorcontrib>Watanabe, Mamoru</creatorcontrib><title>Hepatitis C Virus Nonstructural Protein 5A Inhibits Tumor Necrosis Factor–α–Mediated Apoptosis in Huh7 Cells</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)–α. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-α treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to <50% in Huh7-NS5A compared with control cells. Nuclear factor–κB activation was the same in both cell types, whereas caspase-8, -9, and -3 activity was decreased in Huh7-NS5A cells, compared with control cells, which indicates that the inhibition of caspase-8 activation is responsible for the antiapoptotic effect of the NS5A protein. The coexpression of NS5A did not inhibit apoptosis induced by caspase-8 or Fas-associating death domain protein expression. These findings suggest that the NS5A protein inhibits the apoptotic effect of TNF-α upstream of caspase-8 in the apoptosis cascade</description><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Arabidopsis Proteins - physiology</subject><subject>Biological and medical sciences</subject><subject>Caspase 8</subject><subject>Caspase 9</subject><subject>Caspases - physiology</subject><subject>Cell Line</subject><subject>Chronic hepatitis</subject><subject>Dactinomycin - pharmacology</subject><subject>Fatty Acid Desaturases - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hepacivirus</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - metabolism</subject><subject>Hepatitis C</subject><subject>Hepatitis C - pathology</subject><subject>Hepatitis C virus</subject><subject>Hepatocytes</subject><subject>Hepatocytes - cytology</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>NF-kappa B - physiology</subject><subject>NS5A protein</subject><subject>Nucleic Acid Synthesis Inhibitors - pharmacology</subject><subject>Oligoribonucleotides, Antisense - genetics</subject><subject>Oligoribonucleotides, Antisense - pharmacology</subject><subject>Signal Transduction - immunology</subject><subject>T lymphocytes</subject><subject>Transfection</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><subject>Tumor necrosis factors</subject><subject>Viability</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>Viral Nonstructural Proteins - physiology</subject><subject>Virology</subject><subject>Viruses</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0cFu1DAQANAIgehS4A9ABglugbEd2_FxtaLdrpbCoaCKi-U4juolm6S2I7U3_oEv4Uf4CL4EL1l1JSTExT74zYxnJsueYniDoeRvqZCE0XvZDDMqcs4xvZ_NAAjJcSnlUfYohA0AFJSLh9kRLjgpaAmz7HppBx1ddAEt0Gfnx4DO-y5EP5o4et2ij76P1nWIzdFZd-UqFwO6GLe9R-fW-D6kwBNtYu9_ffv-80c63tva6WhrNB_6If4BKXw5Xgm0sG0bHmcPGt0G-2R_H2efTt5dLJb5-sPp2WK-zk1R0piXjalrySypJVhcFUVVYi6k5XUhSUkssNSNpsKYCmxSYKQFLACobQogDT3OXk95B99fjzZEtXXBpB_ozvZjUALTMg0L_guxJCAZkwm-_Atu-tF3qQlFCJWYcF4esu2GE7xt1ODdVvtbhUHtVqWmVSX4fJ9trLa2PrD9bhJ4tQc6GN02XnfGhYNjlFHMeHIvJtePw7-LPZvMJqRV3SkKIJjgu1r59O5CtDd379p_VVxQwdTy8osSa3m6Wq2wuqS_AQMJvsY</recordid><startdate>20031115</startdate><enddate>20031115</enddate><creator>Miyasaka, Yuka</creator><creator>Enomoto, Nobuyuki</creator><creator>Kurosaki, Masayuki</creator><creator>Sakamoto, Naoya</creator><creator>Kanazawa, Nobuhiko</creator><creator>Kohashi, Takahiro</creator><creator>Ueda, Eri</creator><creator>Maekawa, Shinya</creator><creator>Watanabe, Hideki</creator><creator>Izumi, Namiki</creator><creator>Sato, Chifumi</creator><creator>Watanabe, Mamoru</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><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>K9.</scope><scope>NAPCQ</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20031115</creationdate><title>Hepatitis C Virus Nonstructural Protein 5A Inhibits Tumor Necrosis Factor–α–Mediated Apoptosis in Huh7 Cells</title><author>Miyasaka, Yuka ; Enomoto, Nobuyuki ; Kurosaki, Masayuki ; Sakamoto, Naoya ; Kanazawa, Nobuhiko ; Kohashi, Takahiro ; Ueda, Eri ; Maekawa, Shinya ; Watanabe, Hideki ; Izumi, Namiki ; Sato, Chifumi ; Watanabe, Mamoru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-8fcdd95e2d90e1b44b81679e6d49282e05004a37ccb0ee2d0c9e017003ef402f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Arabidopsis Proteins - physiology</topic><topic>Biological and medical sciences</topic><topic>Caspase 8</topic><topic>Caspase 9</topic><topic>Caspases - physiology</topic><topic>Cell Line</topic><topic>Chronic hepatitis</topic><topic>Dactinomycin - pharmacology</topic><topic>Fatty Acid Desaturases - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hepacivirus</topic><topic>Hepacivirus - genetics</topic><topic>Hepacivirus - metabolism</topic><topic>Hepatitis C</topic><topic>Hepatitis C - pathology</topic><topic>Hepatitis C virus</topic><topic>Hepatocytes</topic><topic>Hepatocytes - cytology</topic><topic>Humans</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>NF-kappa B - physiology</topic><topic>NS5A protein</topic><topic>Nucleic Acid Synthesis Inhibitors - pharmacology</topic><topic>Oligoribonucleotides, Antisense - genetics</topic><topic>Oligoribonucleotides, Antisense - pharmacology</topic><topic>Signal Transduction - immunology</topic><topic>T lymphocytes</topic><topic>Transfection</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><topic>Tumor necrosis factors</topic><topic>Viability</topic><topic>Viral Nonstructural Proteins - genetics</topic><topic>Viral Nonstructural Proteins - physiology</topic><topic>Virology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyasaka, Yuka</creatorcontrib><creatorcontrib>Enomoto, Nobuyuki</creatorcontrib><creatorcontrib>Kurosaki, Masayuki</creatorcontrib><creatorcontrib>Sakamoto, Naoya</creatorcontrib><creatorcontrib>Kanazawa, Nobuhiko</creatorcontrib><creatorcontrib>Kohashi, Takahiro</creatorcontrib><creatorcontrib>Ueda, Eri</creatorcontrib><creatorcontrib>Maekawa, Shinya</creatorcontrib><creatorcontrib>Watanabe, Hideki</creatorcontrib><creatorcontrib>Izumi, Namiki</creatorcontrib><creatorcontrib>Sato, Chifumi</creatorcontrib><creatorcontrib>Watanabe, Mamoru</creatorcontrib><collection>Istex</collection><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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyasaka, Yuka</au><au>Enomoto, Nobuyuki</au><au>Kurosaki, Masayuki</au><au>Sakamoto, Naoya</au><au>Kanazawa, Nobuhiko</au><au>Kohashi, Takahiro</au><au>Ueda, Eri</au><au>Maekawa, Shinya</au><au>Watanabe, Hideki</au><au>Izumi, Namiki</au><au>Sato, Chifumi</au><au>Watanabe, Mamoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis C Virus Nonstructural Protein 5A Inhibits Tumor Necrosis Factor–α–Mediated Apoptosis in Huh7 Cells</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>The Journal of Infectious Diseases</stitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2003-11-15</date><risdate>2003</risdate><volume>188</volume><issue>10</issue><spage>1537</spage><epage>1544</epage><pages>1537-1544</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)–α. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-α treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to <50% in Huh7-NS5A compared with control cells. Nuclear factor–κB activation was the same in both cell types, whereas caspase-8, -9, and -3 activity was decreased in Huh7-NS5A cells, compared with control cells, which indicates that the inhibition of caspase-8 activation is responsible for the antiapoptotic effect of the NS5A protein. The coexpression of NS5A did not inhibit apoptosis induced by caspase-8 or Fas-associating death domain protein expression. These findings suggest that the NS5A protein inhibits the apoptotic effect of TNF-α upstream of caspase-8 in the apoptosis cascade</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>14624380</pmid><doi>10.1086/379253</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2003-11, Vol.188 (10), p.1537-1544 |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Apoptosis Apoptosis - physiology Arabidopsis Proteins - physiology Biological and medical sciences Caspase 8 Caspase 9 Caspases - physiology Cell Line Chronic hepatitis Dactinomycin - pharmacology Fatty Acid Desaturases - physiology Fundamental and applied biological sciences. Psychology Hepacivirus Hepacivirus - genetics Hepacivirus - metabolism Hepatitis C Hepatitis C - pathology Hepatitis C virus Hepatocytes Hepatocytes - cytology Humans Infections Infectious diseases Medical sciences Microbiology Miscellaneous NF-kappa B - physiology NS5A protein Nucleic Acid Synthesis Inhibitors - pharmacology Oligoribonucleotides, Antisense - genetics Oligoribonucleotides, Antisense - pharmacology Signal Transduction - immunology T lymphocytes Transfection Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - physiology Tumor necrosis factors Viability Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - physiology Virology Viruses |
| title | Hepatitis C Virus Nonstructural Protein 5A Inhibits Tumor Necrosis Factor–α–Mediated Apoptosis in Huh7 Cells |
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