Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts
The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl is...
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| Veröffentlicht in: | Pharmacological research 2011-03, Vol.63 (3), p.233-240 |
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| creator | Ernst, Insa M.A. Wagner, Anika E. Schuemann, Christine Storm, Niels Höppner, Wolfgang Döring, Frank Stocker, Achim Rimbach, Gerald |
| description | The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and
in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts. |
| doi_str_mv | 10.1016/j.phrs.2010.11.005 |
| format | Article |
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in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts.</description><identifier>ISSN: 1043-6618</identifier><identifier>EISSN: 1096-1186</identifier><identifier>DOI: 10.1016/j.phrs.2010.11.005</identifier><identifier>PMID: 21109004</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Allyl isothiocyanate ; Animals ; Antioxidant response element (ARE) ; Binding Sites - physiology ; Butyl isothiocyanate ; Cells, Cultured ; ERK ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Isothiocyanates - chemistry ; Isothiocyanates - pharmacology ; Mice ; NF-E2-Related Factor 2 - metabolism ; NIH 3T3 Cells ; Nrf2 ; Phenylethyl isothiocyanate</subject><ispartof>Pharmacological research, 2011-03, Vol.63 (3), p.233-240</ispartof><rights>2010 Elsevier Ltd</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-6a1322de59e217d45c259ed5c773b81f4f6160faa62a9dfc09920b2f7244fa063</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phrs.2010.11.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21109004$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ernst, Insa M.A.</creatorcontrib><creatorcontrib>Wagner, Anika E.</creatorcontrib><creatorcontrib>Schuemann, Christine</creatorcontrib><creatorcontrib>Storm, Niels</creatorcontrib><creatorcontrib>Höppner, Wolfgang</creatorcontrib><creatorcontrib>Döring, Frank</creatorcontrib><creatorcontrib>Stocker, Achim</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><title>Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts</title><title>Pharmacological research</title><addtitle>Pharmacol Res</addtitle><description>The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and
in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts.</description><subject>Allyl isothiocyanate</subject><subject>Animals</subject><subject>Antioxidant response element (ARE)</subject><subject>Binding Sites - physiology</subject><subject>Butyl isothiocyanate</subject><subject>Cells, Cultured</subject><subject>ERK</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Isothiocyanates - chemistry</subject><subject>Isothiocyanates - pharmacology</subject><subject>Mice</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NIH 3T3 Cells</subject><subject>Nrf2</subject><subject>Phenylethyl isothiocyanate</subject><issn>1043-6618</issn><issn>1096-1186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMofv8BD9KbF7vOZNvsFryI-AWiB_Uc0mTCZsm2a5IK--9NWfXoaV6GZ16Yh7EzhAkCiqvlZL0IccJhXOAEoN5hhwiNKBHnYnfM1bQUAucH7CjGJQA0FcI-O-CYMYDqkL3deL_x5WXRDinPQnWmWC-o23hKi7xwsU8L1-uN6lSiQunkvsbwEiwvXFfowachkCmsa0PfehVTPGF7VvlIpz_zmH3c373fPpbPrw9PtzfPpa44plIonHJuqG6I48xUteY5mlrPZtN2jrayAgVYpQRXjbEamoZDy-2MV5VVIKbH7GLbuw7950AxyZWLmrxXHfVDlPMaaoE1QCb5ltShjzGQlevgVipsJIIcXcqlHF3K0aVElNllPjr_qR_aFZm_k195GbjeApSf_HIUZNSOOk3GBdJJmt791_8NplaFZg</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Ernst, Insa M.A.</creator><creator>Wagner, Anika E.</creator><creator>Schuemann, Christine</creator><creator>Storm, Niels</creator><creator>Höppner, Wolfgang</creator><creator>Döring, Frank</creator><creator>Stocker, Achim</creator><creator>Rimbach, Gerald</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20110301</creationdate><title>Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts</title><author>Ernst, Insa M.A. ; Wagner, Anika E. ; Schuemann, Christine ; Storm, Niels ; Höppner, Wolfgang ; Döring, Frank ; Stocker, Achim ; Rimbach, Gerald</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-6a1322de59e217d45c259ed5c773b81f4f6160faa62a9dfc09920b2f7244fa063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allyl isothiocyanate</topic><topic>Animals</topic><topic>Antioxidant response element (ARE)</topic><topic>Binding Sites - physiology</topic><topic>Butyl isothiocyanate</topic><topic>Cells, Cultured</topic><topic>ERK</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Isothiocyanates - chemistry</topic><topic>Isothiocyanates - pharmacology</topic><topic>Mice</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NIH 3T3 Cells</topic><topic>Nrf2</topic><topic>Phenylethyl isothiocyanate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ernst, Insa M.A.</creatorcontrib><creatorcontrib>Wagner, Anika E.</creatorcontrib><creatorcontrib>Schuemann, Christine</creatorcontrib><creatorcontrib>Storm, Niels</creatorcontrib><creatorcontrib>Höppner, Wolfgang</creatorcontrib><creatorcontrib>Döring, Frank</creatorcontrib><creatorcontrib>Stocker, Achim</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ernst, Insa M.A.</au><au>Wagner, Anika E.</au><au>Schuemann, Christine</au><au>Storm, Niels</au><au>Höppner, Wolfgang</au><au>Döring, Frank</au><au>Stocker, Achim</au><au>Rimbach, Gerald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts</atitle><jtitle>Pharmacological research</jtitle><addtitle>Pharmacol Res</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>63</volume><issue>3</issue><spage>233</spage><epage>240</epage><pages>233-240</pages><issn>1043-6618</issn><eissn>1096-1186</eissn><abstract>The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and
in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>21109004</pmid><doi>10.1016/j.phrs.2010.11.005</doi><tpages>8</tpages></addata></record> |
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| subjects | Allyl isothiocyanate Animals Antioxidant response element (ARE) Binding Sites - physiology Butyl isothiocyanate Cells, Cultured ERK Fibroblasts - drug effects Fibroblasts - metabolism Isothiocyanates - chemistry Isothiocyanates - pharmacology Mice NF-E2-Related Factor 2 - metabolism NIH 3T3 Cells Nrf2 Phenylethyl isothiocyanate |
| title | Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts |
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