Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway
The extract and hemiterpene glycosides of Ilex rotunda Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin di...
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| creator | Lee, Da Hee Nam, Yoon Jeong Kim, Yun Jeong Lee, Min Won Lee, Chung Soo |
| description | The extract and hemiterpene glycosides of
Ilex rotunda
Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of rotundarpene on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in the cytosolic levels of Bid, Bcl-2, Bcl-xL, and survivin proteins, increase in the cytosolic levels of Bax, and increase in the mitochondrial levels of VDAC1, loss of the mitochondrial transmembrane potential, release of cytochrome
c
, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with rotundarpene prevented TRAIL-induced changes in the levels of apoptosis-related proteins, formations of reactive oxygen species and nitric oxide, nuclear damage, and cell death. These results suggest that rotundarpene may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species and reactive nitrogen species. These data suggest that rotundarpene appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases. |
| doi_str_mv | 10.1007/s00210-014-1051-8 |
| format | Article |
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Ilex rotunda
Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of rotundarpene on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in the cytosolic levels of Bid, Bcl-2, Bcl-xL, and survivin proteins, increase in the cytosolic levels of Bax, and increase in the mitochondrial levels of VDAC1, loss of the mitochondrial transmembrane potential, release of cytochrome
c
, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with rotundarpene prevented TRAIL-induced changes in the levels of apoptosis-related proteins, formations of reactive oxygen species and nitric oxide, nuclear damage, and cell death. These results suggest that rotundarpene may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species and reactive nitrogen species. These data suggest that rotundarpene appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.</description><identifier>ISSN: 0028-1298</identifier><identifier>EISSN: 1432-1912</identifier><identifier>DOI: 10.1007/s00210-014-1051-8</identifier><identifier>PMID: 25273175</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Activation ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; BAX protein ; Bcl-2 protein ; Bcl-x protein ; BH3 Interacting Domain Death Agonist Protein - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Caffeic Acids - pharmacology ; Caspase ; Caspase 8 - metabolism ; Caspase-8 ; Cell death ; Cell Line ; Cytochrome c ; Cytosol - drug effects ; Cytosol - metabolism ; Glycosides ; Hemiterpenes - pharmacology ; Humans ; Inflammation ; Keratinocytes ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Neurosciences ; Nitric oxide ; Original Article ; p53 Protein ; Pharmacology/Toxicology ; Proteins ; Reactive nitrogen species ; Reactive Nitrogen Species - metabolism ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Skin diseases ; Species ; Survivin ; TNF-Related Apoptosis-Inducing Ligand - administration & dosage ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; TRAIL protein ; Tumor suppressor genes</subject><ispartof>Naunyn-Schmiedeberg's archives of pharmacology, 2014-12, Vol.387 (12), p.1209-1219</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>Naunyn-Schmiedeberg's Archives of Pharmacology is a copyright of Springer, (2014). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-161eb995ada3b8937caa8ce86b3653349e6e7c951a8933b37771f9e1c8460773</citedby><cites>FETCH-LOGICAL-c442t-161eb995ada3b8937caa8ce86b3653349e6e7c951a8933b37771f9e1c8460773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00210-014-1051-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00210-014-1051-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25273175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Da Hee</creatorcontrib><creatorcontrib>Nam, Yoon Jeong</creatorcontrib><creatorcontrib>Kim, Yun Jeong</creatorcontrib><creatorcontrib>Lee, Min Won</creatorcontrib><creatorcontrib>Lee, Chung Soo</creatorcontrib><title>Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway</title><title>Naunyn-Schmiedeberg's archives of pharmacology</title><addtitle>Naunyn-Schmiedeberg's Arch Pharmacol</addtitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><description>The extract and hemiterpene glycosides of
Ilex rotunda
Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of rotundarpene on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in the cytosolic levels of Bid, Bcl-2, Bcl-xL, and survivin proteins, increase in the cytosolic levels of Bax, and increase in the mitochondrial levels of VDAC1, loss of the mitochondrial transmembrane potential, release of cytochrome
c
, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with rotundarpene prevented TRAIL-induced changes in the levels of apoptosis-related proteins, formations of reactive oxygen species and nitric oxide, nuclear damage, and cell death. These results suggest that rotundarpene may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species and reactive nitrogen species. These data suggest that rotundarpene appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.</description><subject>Activation</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Bcl-x protein</subject><subject>BH3 Interacting Domain Death Agonist Protein - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caffeic Acids - pharmacology</subject><subject>Caspase</subject><subject>Caspase 8 - metabolism</subject><subject>Caspase-8</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Cytochrome c</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Glycosides</subject><subject>Hemiterpenes - pharmacology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Keratinocytes</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Neurosciences</subject><subject>Nitric oxide</subject><subject>Original Article</subject><subject>p53 Protein</subject><subject>Pharmacology/Toxicology</subject><subject>Proteins</subject><subject>Reactive nitrogen species</subject><subject>Reactive Nitrogen Species - metabolism</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Skin diseases</subject><subject>Species</subject><subject>Survivin</subject><subject>TNF-Related Apoptosis-Inducing Ligand - administration & dosage</subject><subject>TNF-Related Apoptosis-Inducing Ligand - metabolism</subject><subject>TRAIL protein</subject><subject>Tumor suppressor genes</subject><issn>0028-1298</issn><issn>1432-1912</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kc2KFDEUhYMoTjv6AG4k4MZNNDepSlLLcfBnoEEYeh9SqdvTGbuSMkkp_Ri-sdXTrYLgKpDznZPAR8hL4G-Bc_2ucC6AMw4NA94CM4_IChopGHQgHpPVEhsGojMX5Fkp95xzBW37lFyIVmgJul2Rn7epznFwecKIdMr4HWMtdHN7dbNmIQ6zx4G6KU01lVBoiHQ3jy7Sr5hdDTH5Q8VC-wMt87S0SwnxjtYdUu_K5Aoyw6iLA30fBja5uvvhDuXh4siMoSa_S3HIwe3pOX5OnmzdvuCL83lJNh8_bK4_s_WXTzfXV2vmm0ZUBgqw77rWDU72ppPaO2c8GtVL1UrZdKhQ-64Ft4Syl1pr2HYI3jSKay0vyZvT7JTTtxlLtWMoHvd7FzHNxYISClTbaLOgr_9B79Oc4_I5K3gjpVTmgYIT5XMqJePWTjmMLh8scHvUZU-67KLLHnXZY-fVeXnuRxz-NH77WQBxAsoSxTvMf5_-_-ovuPmhGQ</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Lee, Da Hee</creator><creator>Nam, Yoon Jeong</creator><creator>Kim, Yun Jeong</creator><creator>Lee, Min Won</creator><creator>Lee, Chung Soo</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20141201</creationdate><title>Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway</title><author>Lee, Da Hee ; Nam, Yoon Jeong ; Kim, Yun Jeong ; Lee, Min Won ; Lee, Chung Soo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-161eb995ada3b8937caa8ce86b3653349e6e7c951a8933b37771f9e1c8460773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activation</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>Bcl-x protein</topic><topic>BH3 Interacting Domain Death Agonist Protein - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Caffeic Acids - pharmacology</topic><topic>Caspase</topic><topic>Caspase 8 - metabolism</topic><topic>Caspase-8</topic><topic>Cell death</topic><topic>Cell Line</topic><topic>Cytochrome c</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Glycosides</topic><topic>Hemiterpenes - pharmacology</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Keratinocytes</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Neurosciences</topic><topic>Nitric oxide</topic><topic>Original Article</topic><topic>p53 Protein</topic><topic>Pharmacology/Toxicology</topic><topic>Proteins</topic><topic>Reactive nitrogen species</topic><topic>Reactive Nitrogen Species - metabolism</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Skin diseases</topic><topic>Species</topic><topic>Survivin</topic><topic>TNF-Related Apoptosis-Inducing Ligand - administration & dosage</topic><topic>TNF-Related Apoptosis-Inducing Ligand - metabolism</topic><topic>TRAIL protein</topic><topic>Tumor suppressor genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Da Hee</creatorcontrib><creatorcontrib>Nam, Yoon Jeong</creatorcontrib><creatorcontrib>Kim, Yun Jeong</creatorcontrib><creatorcontrib>Lee, Min Won</creatorcontrib><creatorcontrib>Lee, Chung Soo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Da Hee</au><au>Nam, Yoon Jeong</au><au>Kim, Yun Jeong</au><au>Lee, Min Won</au><au>Lee, Chung Soo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway</atitle><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle><stitle>Naunyn-Schmiedeberg's Arch Pharmacol</stitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>387</volume><issue>12</issue><spage>1209</spage><epage>1219</epage><pages>1209-1219</pages><issn>0028-1298</issn><eissn>1432-1912</eissn><abstract>The extract and hemiterpene glycosides of
Ilex rotunda
Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of rotundarpene on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in the cytosolic levels of Bid, Bcl-2, Bcl-xL, and survivin proteins, increase in the cytosolic levels of Bax, and increase in the mitochondrial levels of VDAC1, loss of the mitochondrial transmembrane potential, release of cytochrome
c
, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with rotundarpene prevented TRAIL-induced changes in the levels of apoptosis-related proteins, formations of reactive oxygen species and nitric oxide, nuclear damage, and cell death. These results suggest that rotundarpene may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species and reactive nitrogen species. These data suggest that rotundarpene appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>25273175</pmid><doi>10.1007/s00210-014-1051-8</doi><tpages>11</tpages></addata></record> |
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| subjects | Activation Antioxidants Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein Bcl-x protein BH3 Interacting Domain Death Agonist Protein - metabolism Biomedical and Life Sciences Biomedicine Caffeic Acids - pharmacology Caspase Caspase 8 - metabolism Caspase-8 Cell death Cell Line Cytochrome c Cytosol - drug effects Cytosol - metabolism Glycosides Hemiterpenes - pharmacology Humans Inflammation Keratinocytes Keratinocytes - drug effects Keratinocytes - metabolism Membrane potential Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondria - metabolism Neurosciences Nitric oxide Original Article p53 Protein Pharmacology/Toxicology Proteins Reactive nitrogen species Reactive Nitrogen Species - metabolism Reactive oxygen species Reactive Oxygen Species - metabolism Skin diseases Species Survivin TNF-Related Apoptosis-Inducing Ligand - administration & dosage TNF-Related Apoptosis-Inducing Ligand - metabolism TRAIL protein Tumor suppressor genes |
| title | Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway |
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