Thujaplicin–copper chelates inhibit replication of human influenza viruses
Identifieur interne : 000197 ( Istex/Corpus ); précédent : 000196; suivant : 000198Thujaplicin–copper chelates inhibit replication of human influenza viruses
Auteurs : Daisei Miyamoto ; Yuki Kusagaya ; Naoko Endo ; Ayako Sometani ; Seiji Takeo ; Takashi Suzuki ; Yaeno Arima ; Katsuyuki Nakajima ; Yasuo SuzukiSource :
- Antiviral Research [ 0166-3542 ] ; 1998.
English descriptors
- Teeft :
- Anti6iral, Anti6iral research, Apoptosis, Apoptotic, Assay, Canine kidney, Cell death, Cell growth, Cell viability, Chelate, Chem, Copper chelate, Copper chelates, Copper ions, Copper sulfate, Culture medium, Cytometric, Cytometric analysis, Cytotoxic, Cytotoxic effects, Early phase, Early stage, Hela cells, Host cells, Human apoptosis, Inhibitory effects, Lactate dehydrogenase, Mdck, Mdck cells, Metal chelates, Miyamoto, Morphological changes, Postinfection, Supernatant, Suzuki, Takizawa, Test samples, Thuja plicata, Thujaplicin, Thujaplicin copper chelates, Thujaplicins, Total cells, Viral, Viral infection, Virus, Virus infection, Zinc ions.
Abstract
Abstract: The effects of α-, β- and γ-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 μM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.
Url:
DOI: 10.1016/S0166-3542(98)00034-5
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Thujaplicin–copper chelates inhibit replication of human influenza viruses</title><author><name sortKey="Miyamoto, Daisei" sort="Miyamoto, Daisei" uniqKey="Miyamoto D" first="Daisei" last="Miyamoto">Daisei Miyamoto</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kusagaya, Yuki" sort="Kusagaya, Yuki" uniqKey="Kusagaya Y" first="Yuki" last="Kusagaya">Yuki Kusagaya</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Endo, Naoko" sort="Endo, Naoko" uniqKey="Endo N" first="Naoko" last="Endo">Naoko Endo</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Sometani, Ayako" sort="Sometani, Ayako" uniqKey="Sometani A" first="Ayako" last="Sometani">Ayako Sometani</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Seiji Takeo" sort="Seiji Takeo" uniqKey="Seiji Takeo" first="" last="Seiji Takeo">Seiji Takeo</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Suzuki, Takashi" sort="Suzuki, Takashi" uniqKey="Suzuki T" first="Takashi" 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Suzuki">Yasuo Suzuki</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:735996364087205C257469F4F7F05747D82AF949</idno><date when="1998" year="1998">1998</date><idno type="doi">10.1016/S0166-3542(98)00034-5</idno><idno type="url">https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000197</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000197</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Thujaplicin–copper chelates inhibit replication of human influenza viruses</title><author><name sortKey="Miyamoto, Daisei" sort="Miyamoto, Daisei" uniqKey="Miyamoto D" first="Daisei" last="Miyamoto">Daisei Miyamoto</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kusagaya, Yuki" sort="Kusagaya, Yuki" uniqKey="Kusagaya Y" first="Yuki" last="Kusagaya">Yuki Kusagaya</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Endo, Naoko" sort="Endo, Naoko" uniqKey="Endo N" first="Naoko" last="Endo">Naoko Endo</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Sometani, Ayako" sort="Sometani, Ayako" uniqKey="Sometani A" first="Ayako" last="Sometani">Ayako Sometani</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Seiji Takeo" sort="Seiji Takeo" uniqKey="Seiji Takeo" first="" last="Seiji Takeo">Seiji Takeo</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Suzuki, Takashi" sort="Suzuki, Takashi" uniqKey="Suzuki T" first="Takashi" last="Suzuki">Takashi Suzuki</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author><author><name sortKey="Arima, Yaeno" sort="Arima, Yaeno" uniqKey="Arima Y" first="Yaeno" last="Arima">Yaeno Arima</name><affiliation><mods:affiliation>Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamasina-ku, Kyoto 607, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakajima, Katsuyuki" sort="Nakajima, Katsuyuki" uniqKey="Nakajima K" first="Katsuyuki" last="Nakajima">Katsuyuki Nakajima</name><affiliation><mods:affiliation>Otsuka America Pharmaceutical, Inc., 2440, Research Boulourd, Lock Ville, MD 20850, USA</mods:affiliation></affiliation></author><author><name sortKey="Yasuo Suzuki" sort="Yasuo Suzuki" uniqKey="Yasuo Suzuki" first="" last="Yasuo Suzuki">Yasuo Suzuki</name><affiliation><mods:affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Antiviral Research</title><title level="j" type="abbrev">AVR</title><idno type="ISSN">0166-3542</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">39</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="89">89</biblScope><biblScope unit="page" to="100">100</biblScope></imprint><idno type="ISSN">0166-3542</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0166-3542</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Anti6iral</term><term>Anti6iral research</term><term>Apoptosis</term><term>Apoptotic</term><term>Assay</term><term>Canine kidney</term><term>Cell death</term><term>Cell growth</term><term>Cell viability</term><term>Chelate</term><term>Chem</term><term>Copper chelate</term><term>Copper chelates</term><term>Copper ions</term><term>Copper sulfate</term><term>Culture medium</term><term>Cytometric</term><term>Cytometric analysis</term><term>Cytotoxic</term><term>Cytotoxic effects</term><term>Early phase</term><term>Early stage</term><term>Hela cells</term><term>Host cells</term><term>Human apoptosis</term><term>Inhibitory effects</term><term>Lactate dehydrogenase</term><term>Mdck</term><term>Mdck cells</term><term>Metal chelates</term><term>Miyamoto</term><term>Morphological changes</term><term>Postinfection</term><term>Supernatant</term><term>Suzuki</term><term>Takizawa</term><term>Test samples</term><term>Thuja plicata</term><term>Thujaplicin</term><term>Thujaplicin copper chelates</term><term>Thujaplicins</term><term>Total cells</term><term>Viral</term><term>Viral infection</term><term>Virus</term><term>Virus infection</term><term>Zinc ions</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The effects of α-, β- and γ-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 μM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>chelate</json:string><json:string>apoptosis</json:string><json:string>mdck</json:string><json:string>mdck cells</json:string><json:string>thujaplicin</json:string><json:string>copper chelates</json:string><json:string>thujaplicins</json:string><json:string>viral</json:string><json:string>metal chelates</json:string><json:string>miyamoto</json:string><json:string>takizawa</json:string><json:string>copper chelate</json:string><json:string>anti6iral research</json:string><json:string>cytometric</json:string><json:string>anti6iral</json:string><json:string>inhibitory effects</json:string><json:string>cytotoxic</json:string><json:string>postinfection</json:string><json:string>apoptotic</json:string><json:string>cytometric analysis</json:string><json:string>copper ions</json:string><json:string>chem</json:string><json:string>cell death</json:string><json:string>thujaplicin copper chelates</json:string><json:string>culture medium</json:string><json:string>viral infection</json:string><json:string>host cells</json:string><json:string>early stage</json:string><json:string>cell viability</json:string><json:string>suzuki</json:string><json:string>virus infection</json:string><json:string>cytotoxic effects</json:string><json:string>assay</json:string><json:string>supernatant</json:string><json:string>lactate dehydrogenase</json:string><json:string>human apoptosis</json:string><json:string>canine kidney</json:string><json:string>hela cells</json:string><json:string>test samples</json:string><json:string>morphological changes</json:string><json:string>total cells</json:string><json:string>copper sulfate</json:string><json:string>early phase</json:string><json:string>thuja plicata</json:string><json:string>cell growth</json:string><json:string>zinc ions</json:string><json:string>virus</json:string></teeft></keywords><author><json:item><name>Daisei Miyamoto</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Yuki Kusagaya</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Naoko Endo</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Ayako Sometani</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Seiji Takeo</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Takashi Suzuki</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item><json:item><name>Yaeno Arima</name><affiliations><json:string>Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamasina-ku, Kyoto 607, Japan</json:string></affiliations></json:item><json:item><name>Katsuyuki Nakajima</name><affiliations><json:string>Otsuka America Pharmaceutical, Inc., 2440, Research Boulourd, Lock Ville, MD 20850, USA</json:string></affiliations></json:item><json:item><name>Yasuo Suzuki</name><affiliations><json:string>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Antiviral effect</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Apoptosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Influenza virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Thujaplicin–metal chelates</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>BSA, bovine serum albumin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ED50, 50% effective dose</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EMEM, Eagle's minimal essential medium</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FCS, fetal calf serum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HBSS, Hank's buffered saline solution</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LDH, lactate dehydrogenase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MDCK, Madin–Darby canine kidney</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PBS, phosphate buffered saline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PI, propidium iodide</value></json:item></subject><arkIstex>ark:/67375/6H6-2DGLS83N-8</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: The effects of α-, β- and γ-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 μM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.</abstract><qualityIndicators><score>8.907</score><pdfWordCount>4987</pdfWordCount><pdfCharCount>32515</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>12</pdfPageCount><pdfPageSize>535 x 675 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>160</abstractWordCount><abstractCharCount>1160</abstractCharCount><keywordCount>13</keywordCount></qualityIndicators><title>Thujaplicin–copper chelates inhibit replication of human influenza viruses</title><pmid><json:string>9806486</json:string></pmid><pii><json:string>S0166-3542(98)00034-5</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Antiviral Research</title><language><json:string>unknown</json:string></language><publicationDate>1998</publicationDate><issn><json:string>0166-3542</json:string></issn><pii><json:string>S0166-3542(00)X0038-1</json:string></pii><volume>39</volume><issue>2</issue><pages><first>89</first><last>100</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1998</json:string></date><geogName></geogName><orgName><json:string>Department of Analytical</json:string><json:string>Takasago</json:string><json:string>Research Boulourd</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>In</json:string><json:string>Recent</json:string></persName><placeName><json:string>Kyoto</json:string><json:string>Shizuoka</json:string><json:string>Japan</json:string><json:string>Tokyo</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>McCloskey et al., 1994</json:string><json:string>Anderson and Gripenberg, 1948</json:string><json:string>Yamato et al. (1986)</json:string><json:string>Akers et al., 1980</json:string><json:string>Inomori et al. (1993)</json:string><json:string>MacLean and Gardner, 1956</json:string><json:string>Suzuki et al., 1983</json:string><json:string>Hinshaw et al. (1994)</json:string><json:string>Inomori et al., 1993</json:string><json:string>Takizawa et al., 1993</json:string><json:string>Cohen and Duke, 1984</json:string><json:string>Mori et al., 1995</json:string><json:string>Trust and Coombs, 1973</json:string><json:string>Yamato et al., 1986</json:string><json:string>Hinshaw et al., 1994</json:string><json:string>Takizawa et al. (1993, 1995)</json:string><json:string>Okabe et al., 1988</json:string><json:string>Takeda et al., 1993</json:string><json:string>Muto et al., 1995</json:string><json:string>Olsen et al. (1996)</json:string><json:string>Suzuki et al., 1980</json:string><json:string>Otsuka America Pharmaceutical, Inc., 2440</json:string><json:string>Suzuki et al., 1996</json:string><json:string>Endo et al., 1988</json:string><json:string>Edman and Gripenberg, 1948</json:string><json:string>Olsen et al., 1996</json:string><json:string>Kontoghiorghes et al. (1986)</json:string><json:string>D. Miyamoto et al.</json:string><json:string>Takizawa et al., 1995</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-2DGLS83N-8</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - virology</json:string><json:string>2 - pharmacology & pharmacy</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - virology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Virology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Pharmacology, Toxicology and Pharmaceutics</json:string><json:string>3 - Pharmacology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - pathologie infectieuse</json:string></inist></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0166-3542(98)00034-5</json:string></doi><id>735996364087205C257469F4F7F05747D82AF949</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a">Thujaplicin–copper chelates inhibit replication of human influenza viruses</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©1998 Elsevier Science B.V.</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>1998</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Fig. 1: The effect of β-thujaplicin and the copper chelate on apoptosis induced in MDCK cells infected with influenza A/Aichi/2/68(H3N2) virus by gel electrophoresis and flow cytometric analysis. MDCK cells (1×106 cells) were infected for 60 min with influenza A/Aichi/2/68(H3N2) virus at m.o.i. of 20 (a, c), or were mock-infected (b), and further incubated for 40 h (a) or 16 h (b, c) in culture medium alone. To examine the effects of β-thujaplicin alone and β-thujaplicin–copper chelate, the MDCK cells infected with the virus at m.o.i. of 20 (d, f) or without the virus (e) were incubated for 16 h in the medium containing 10 μM of β-thujaplicin alone (d) or 10 μM of β-thujaplicin–copper chelate (e, f). PI-stained cells and DNAs were prepared as described in Section 2, and identical samples were simultaneously analyzed by flow cytometry and gel electrophoresis. DNAs (1×106 cells equivalent) were separated by 1.6% agarose gel electrophoresis followed by staining with ethidium bromide. Fluorescence intensities of cells in G2/M phase (1), G1 phase (2) and apoptotic phase (3) are shown. Ao, percentage of apoptotic to total cells.</note><note type="content">Fig. 2: Synergistic effects of β-thujaplicin and copper ions on apoptosis induced in MDCK cells infected with influenza viruses, assessed by flow cytometric analysis. MDCK cells (1×106 cells) were infected with influenza A/Aichi/2/68(H3N2) (•), A/PEV8/34(H1N1) (○), A/Shingapol/1/57(H2N2) (□) and B/Lee/40 (■) viruses for 60 min with m.o.i. of 20. After the incubation, cells were washed with PBS, and then incubated for 16 h in culture medium containing β-thujaplicin (10 μM) and copper sulfate (0–20 μM). The mock-infected MDCK cells were also incubated for 16 h in culture medium containing 10 μM β-thujaplicin (▴), 5 μM copper sulfate (▵), or 10 μM β-thujaplicin–copper chelate (♦). After the incubation, the numbers of apoptotic cells were determined by flow cytometric analysis using PI staining. Percentages of apoptotic to total cells are shown. Values are the means of three independent determinations; bars, S.D.</note><note type="content">Fig. 3: Effect of time of β-thujaplicin–copper chelate addition on apoptosis induced with influenza viruses. MDCK cells (1×106 cells) were mock-infected or infected with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2) A/Aichi/2/68(H3N2) and B/Lee/40 viruses for 60 min with m.o.i. of 20. For the virus-infected cells, 10 μM β-thujaplicin–copper chelate was added to the medium at 0, 2, 4 or 8 h postinfection. In mock-infected cells, β-thujaplicin–copper chelate was added to the medium at 0 h (+); (–) indicates samples without β-thujaplicin–copper chelate treatment. After the incubation, numbers of apoptotic cells were determined by flow cytometric analysis using PI staining. Percentages of apoptotic to total cells are shown. Values are the means of three independent determinations; bars, S.D.</note><note type="content">Table 1: Inhibition of human influenza A/Aichi/2/68(H3N2) virus-induced apoptosis by thujaplicins and thujaplicin–metal chelates</note><note type="content">Table 2: Effects of β-thujaplicin–copper chelate and β-thujaplicin–zinc chelate on apoptosis induced in MDCK cells infected with various types of influenza viruses</note><note type="content">Table 3: Inhibitiion of the release of influenza viruses during influenza virus-induced apoptosis</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Thujaplicin–copper chelates inhibit replication of human influenza viruses</title><author xml:id="author-0000"><persName><forename type="first">Daisei</forename><surname>Miyamoto</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Yuki</forename><surname>Kusagaya</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Naoko</forename><surname>Endo</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Ayako</forename><surname>Sometani</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0004"><persName><surname>Seiji Takeo</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Takashi</forename><surname>Suzuki</surname></persName><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Yaeno</forename><surname>Arima</surname></persName><affiliation>Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamasina-ku, Kyoto 607, Japan</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Katsuyuki</forename><surname>Nakajima</surname></persName><affiliation>Otsuka America Pharmaceutical, Inc., 2440, Research Boulourd, Lock Ville, MD 20850, USA</affiliation></author><author xml:id="author-0008"><persName><surname>Yasuo Suzuki</surname></persName><note type="correspondence"><p>Corresponding author. Tel.: +81 54 2645725; fax: +81 54 2645721; e-mail:suzukiy@ys2.u-shizuoka-ken.ac.jp</p></note><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation></author><idno type="istex">735996364087205C257469F4F7F05747D82AF949</idno><idno type="ark">ark:/67375/6H6-2DGLS83N-8</idno><idno type="DOI">10.1016/S0166-3542(98)00034-5</idno><idno type="PII">S0166-3542(98)00034-5</idno></analytic><monogr><title level="j">Antiviral Research</title><title level="j" type="abbrev">AVR</title><idno type="pISSN">0166-3542</idno><idno type="PII">S0166-3542(00)X0038-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">39</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="89">89</biblScope><biblScope unit="page" to="100">100</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The effects of α-, β- and γ-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 μM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Antiviral effect</term></item><item><term>Apoptosis</term></item><item><term>Influenza virus</term></item><item><term>Thujaplicin–metal chelates</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>BSA, bovine serum albumin</term></item><item><term>ED50, 50% effective dose</term></item><item><term>EMEM, Eagle's minimal essential medium</term></item><item><term>FCS, fetal calf serum</term></item><item><term>HBSS, Hank's buffered saline solution</term></item><item><term>LDH, lactate dehydrogenase</term></item><item><term>MDCK, Madin–Darby canine kidney</term></item><item><term>PBS, phosphate buffered saline</term></item><item><term>PI, propidium iodide</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>AVR</jid><aid>1439</aid><ce:pii>S0166-3542(98)00034-5</ce:pii><ce:doi>10.1016/S0166-3542(98)00034-5</ce:doi><ce:copyright year="1998" type="full-transfer">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>Thujaplicin–copper chelates inhibit replication of human influenza viruses</ce:title><ce:author-group><ce:author><ce:given-name>Daisei</ce:given-name><ce:surname>Miyamoto</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Yuki</ce:given-name><ce:surname>Kusagaya</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Naoko</ce:given-name><ce:surname>Endo</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Ayako</ce:given-name><ce:surname>Sometani</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:surname>Seiji Takeo</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Takashi</ce:given-name><ce:surname>Suzuki</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Yaeno</ce:given-name><ce:surname>Arima</ce:surname><ce:cross-ref refid="AFF2">b</ce:cross-ref></ce:author><ce:author><ce:given-name>Katsuyuki</ce:given-name><ce:surname>Nakajima</ce:surname><ce:cross-ref refid="AFF3">c</ce:cross-ref></ce:author><ce:author><ce:surname>Yasuo Suzuki</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamasina-ku, Kyoto 607, Japan</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Otsuka America Pharmaceutical, Inc., 2440, Research Boulourd, Lock Ville, MD 20850, USA</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +81 54 2645725; fax: +81 54 2645721; e-mail:suzukiy@ys2.u-shizuoka-ken.ac.jp</ce:text></ce:correspondence></ce:author-group><ce:date-received day="26" month="8" year="1997"></ce:date-received><ce:date-accepted day="8" month="6" year="1998"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The effects of <ce:italic>α</ce:italic>-, <ce:italic>β</ce:italic>- and <ce:italic>γ</ce:italic>-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 <ce:italic>μ</ce:italic>M. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Antiviral effect</ce:text></ce:keyword><ce:keyword><ce:text>Apoptosis</ce:text></ce:keyword><ce:keyword><ce:text>Influenza virus</ce:text></ce:keyword><ce:keyword><ce:text>Thujaplicin–metal chelates</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>BSA, bovine serum albumin</ce:text></ce:keyword><ce:keyword><ce:text>ED<ce:inf>50</ce:inf>, 50% effective dose</ce:text></ce:keyword><ce:keyword><ce:text>EMEM, Eagle's minimal essential medium</ce:text></ce:keyword><ce:keyword><ce:text>FCS, fetal calf serum</ce:text></ce:keyword><ce:keyword><ce:text>HBSS, Hank's buffered saline solution</ce:text></ce:keyword><ce:keyword><ce:text>LDH, lactate dehydrogenase</ce:text></ce:keyword><ce:keyword><ce:text>MDCK, Madin–Darby canine kidney</ce:text></ce:keyword><ce:keyword><ce:text>PBS, phosphate buffered saline</ce:text></ce:keyword><ce:keyword><ce:text>PI, propidium iodide</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Thujaplicin–copper chelates inhibit replication of human influenza viruses</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Thujaplicin–copper chelates inhibit replication of human influenza viruses</title></titleInfo><name type="personal"><namePart type="given">Daisei</namePart><namePart type="family">Miyamoto</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yuki</namePart><namePart type="family">Kusagaya</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Naoko</namePart><namePart type="family">Endo</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ayako</namePart><namePart type="family">Sometani</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="family">Seiji Takeo</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Takashi</namePart><namePart type="family">Suzuki</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yaeno</namePart><namePart type="family">Arima</namePart><affiliation>Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamasina-ku, Kyoto 607, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katsuyuki</namePart><namePart type="family">Nakajima</namePart><affiliation>Otsuka America Pharmaceutical, Inc., 2440, Research Boulourd, Lock Ville, MD 20850, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="family">Yasuo Suzuki</namePart><affiliation>Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan</affiliation><description>Corresponding author. Tel.: +81 54 2645725; fax: +81 54 2645721; e-mail:suzukiy@ys2.u-shizuoka-ken.ac.jp</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The effects of α-, β- and γ-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin–Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin–copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 μM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2–4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin–copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.</abstract><note type="content">Fig. 1: The effect of β-thujaplicin and the copper chelate on apoptosis induced in MDCK cells infected with influenza A/Aichi/2/68(H3N2) virus by gel electrophoresis and flow cytometric analysis. MDCK cells (1×106 cells) were infected for 60 min with influenza A/Aichi/2/68(H3N2) virus at m.o.i. of 20 (a, c), or were mock-infected (b), and further incubated for 40 h (a) or 16 h (b, c) in culture medium alone. To examine the effects of β-thujaplicin alone and β-thujaplicin–copper chelate, the MDCK cells infected with the virus at m.o.i. of 20 (d, f) or without the virus (e) were incubated for 16 h in the medium containing 10 μM of β-thujaplicin alone (d) or 10 μM of β-thujaplicin–copper chelate (e, f). PI-stained cells and DNAs were prepared as described in Section 2, and identical samples were simultaneously analyzed by flow cytometry and gel electrophoresis. DNAs (1×106 cells equivalent) were separated by 1.6% agarose gel electrophoresis followed by staining with ethidium bromide. Fluorescence intensities of cells in G2/M phase (1), G1 phase (2) and apoptotic phase (3) are shown. Ao, percentage of apoptotic to total cells.</note><note type="content">Fig. 2: Synergistic effects of β-thujaplicin and copper ions on apoptosis induced in MDCK cells infected with influenza viruses, assessed by flow cytometric analysis. MDCK cells (1×106 cells) were infected with influenza A/Aichi/2/68(H3N2) (•), A/PEV8/34(H1N1) (○), A/Shingapol/1/57(H2N2) (□) and B/Lee/40 (■) viruses for 60 min with m.o.i. of 20. After the incubation, cells were washed with PBS, and then incubated for 16 h in culture medium containing β-thujaplicin (10 μM) and copper sulfate (0–20 μM). The mock-infected MDCK cells were also incubated for 16 h in culture medium containing 10 μM β-thujaplicin (▴), 5 μM copper sulfate (▵), or 10 μM β-thujaplicin–copper chelate (♦). After the incubation, the numbers of apoptotic cells were determined by flow cytometric analysis using PI staining. Percentages of apoptotic to total cells are shown. Values are the means of three independent determinations; bars, S.D.</note><note type="content">Fig. 3: Effect of time of β-thujaplicin–copper chelate addition on apoptosis induced with influenza viruses. MDCK cells (1×106 cells) were mock-infected or infected with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2) A/Aichi/2/68(H3N2) and B/Lee/40 viruses for 60 min with m.o.i. of 20. For the virus-infected cells, 10 μM β-thujaplicin–copper chelate was added to the medium at 0, 2, 4 or 8 h postinfection. In mock-infected cells, β-thujaplicin–copper chelate was added to the medium at 0 h (+); (–) indicates samples without β-thujaplicin–copper chelate treatment. After the incubation, numbers of apoptotic cells were determined by flow cytometric analysis using PI staining. Percentages of apoptotic to total cells are shown. Values are the means of three independent determinations; bars, S.D.</note><note type="content">Table 1: Inhibition of human influenza A/Aichi/2/68(H3N2) virus-induced apoptosis by thujaplicins and thujaplicin–metal chelates</note><note type="content">Table 2: Effects of β-thujaplicin–copper chelate and β-thujaplicin–zinc chelate on apoptosis induced in MDCK cells infected with various types of influenza viruses</note><note type="content">Table 3: Inhibitiion of the release of influenza viruses during influenza virus-induced apoptosis</note><subject><genre>Keywords</genre><topic>Antiviral effect</topic><topic>Apoptosis</topic><topic>Influenza virus</topic><topic>Thujaplicin–metal chelates</topic></subject><subject><genre>Abbreviations</genre><topic>BSA, bovine serum albumin</topic><topic>ED50, 50% effective dose</topic><topic>EMEM, Eagle's minimal essential medium</topic><topic>FCS, fetal calf serum</topic><topic>HBSS, Hank's buffered saline solution</topic><topic>LDH, lactate dehydrogenase</topic><topic>MDCK, Madin–Darby canine kidney</topic><topic>PBS, phosphate buffered saline</topic><topic>PI, propidium iodide</topic></subject><relatedItem type="host"><titleInfo><title>Antiviral Research</title></titleInfo><titleInfo type="abbreviated"><title>AVR</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued></originInfo><identifier type="ISSN">0166-3542</identifier><identifier type="PII">S0166-3542(00)X0038-1</identifier><part><date>1998</date><detail type="volume"><number>39</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue-pages"><start>63</start><end>140</end></extent><extent unit="pages"><start>89</start><end>100</end></extent></part></relatedItem><identifier type="istex">735996364087205C257469F4F7F05747D82AF949</identifier><identifier type="ark">ark:/67375/6H6-2DGLS83N-8</identifier><identifier type="DOI">10.1016/S0166-3542(98)00034-5</identifier><identifier type="PII">S0166-3542(98)00034-5</identifier><accessCondition type="use and reproduction" contentType="copyright">©1998 Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science B.V., ©1998</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-2DGLS83N-8/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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