Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes
Chronic UVR-exposure may impair the stress response and antioxidant defense mechanisms of human skin. The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane...
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| Veröffentlicht in: | Pharmacological research 2013-12, Vol.78, p.28-40 |
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| creator | Kleszczyński, Konrad Ernst, Insa M.A. Wagner, Anika E. Kruse, Nathalie Zillikens, Detlef Rimbach, Gerald Fischer, Tobias W. |
| description | Chronic UVR-exposure may impair the stress response and antioxidant defense mechanisms of human skin. The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced oxidative stress and apoptosis in ex vivo human full-thickness skin combined with in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction of genes coding for Nrf2-dependent phase II antioxidative enzymes (γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes. Comparative investigations in human ex vivo skin were conducted for analysis of gene expression of above mentioned phase II enzymes and catalase (CAT) as well as hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR exposure of human skin (300mJ/cm2) resulted in a significant time-dependent increase of the number of sunburn cells and caspase-3 activation as biomarkers of apoptosis for up to 48h (p |
| doi_str_mv | 10.1016/j.phrs.2013.09.009 |
| format | Article |
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The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced oxidative stress and apoptosis in ex vivo human full-thickness skin combined with in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction of genes coding for Nrf2-dependent phase II antioxidative enzymes (γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes. Comparative investigations in human ex vivo skin were conducted for analysis of gene expression of above mentioned phase II enzymes and catalase (CAT) as well as hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR exposure of human skin (300mJ/cm2) resulted in a significant time-dependent increase of the number of sunburn cells and caspase-3 activation as biomarkers of apoptosis for up to 48h (p<0.001) and induced a significant decrease of the antioxidant enzyme catalase (p<0.001). This was significantly counteracted by the pre-treatment of human skin with SFN and PEITC (5μM and 10μM). Mechanistic cell culture studies revealed SFN and PEITC to increase Nrf2 activity and Nrf2-dependent gene expression (γGCS, HO-1, NQO1); this was paralleled in human full skin mRNA. In conclusion, the induction of Nrf2-dependent antioxidant pathways seems to be a potential mechanism by which SFN and PEITC protect against UVR-induced oxidative stress and apoptosis in human skin.</description><identifier>ISSN: 1043-6618</identifier><identifier>EISSN: 1096-1186</identifier><identifier>DOI: 10.1016/j.phrs.2013.09.009</identifier><identifier>PMID: 24121007</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Anticarcinogenic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Caspase 3 - metabolism ; Catalase - metabolism ; Cell Line ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - radiation effects ; Humans ; Isothiocyanates - pharmacology ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Nrf2 ; Oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - radiation effects ; Phenylethyl isothiocyanate ; Skin ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; Skin - radiation effects ; Sulforaphane ; Ultraviolet Rays ; UVR</subject><ispartof>Pharmacological research, 2013-12, Vol.78, p.28-40</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-633428f800299b273e3550c3dceabb5dbd8f266776d89727cd9bf802de5655653</citedby><cites>FETCH-LOGICAL-c455t-633428f800299b273e3550c3dceabb5dbd8f266776d89727cd9bf802de5655653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phrs.2013.09.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24121007$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kleszczyński, Konrad</creatorcontrib><creatorcontrib>Ernst, Insa M.A.</creatorcontrib><creatorcontrib>Wagner, Anika E.</creatorcontrib><creatorcontrib>Kruse, Nathalie</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><creatorcontrib>Fischer, Tobias W.</creatorcontrib><title>Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes</title><title>Pharmacological research</title><addtitle>Pharmacol Res</addtitle><description>Chronic UVR-exposure may impair the stress response and antioxidant defense mechanisms of human skin. The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced oxidative stress and apoptosis in ex vivo human full-thickness skin combined with in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction of genes coding for Nrf2-dependent phase II antioxidative enzymes (γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes. Comparative investigations in human ex vivo skin were conducted for analysis of gene expression of above mentioned phase II enzymes and catalase (CAT) as well as hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR exposure of human skin (300mJ/cm2) resulted in a significant time-dependent increase of the number of sunburn cells and caspase-3 activation as biomarkers of apoptosis for up to 48h (p<0.001) and induced a significant decrease of the antioxidant enzyme catalase (p<0.001). This was significantly counteracted by the pre-treatment of human skin with SFN and PEITC (5μM and 10μM). Mechanistic cell culture studies revealed SFN and PEITC to increase Nrf2 activity and Nrf2-dependent gene expression (γGCS, HO-1, NQO1); this was paralleled in human full skin mRNA. In conclusion, the induction of Nrf2-dependent antioxidant pathways seems to be a potential mechanism by which SFN and PEITC protect against UVR-induced oxidative stress and apoptosis in human skin.</description><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Caspase 3 - metabolism</subject><subject>Catalase - metabolism</subject><subject>Cell Line</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>Humans</subject><subject>Isothiocyanates - pharmacology</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nrf2</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - radiation effects</subject><subject>Phenylethyl isothiocyanate</subject><subject>Skin</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Skin - radiation effects</subject><subject>Sulforaphane</subject><subject>Ultraviolet Rays</subject><subject>UVR</subject><issn>1043-6618</issn><issn>1096-1186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1v1iAYhhujcXP6BzwwHHrSCrSlxXhiFr-SRZPpPCUUnq68toBAl9V_5T-U7p0empBAwnXf4eEqiucEVwQT9upQ-SnEimJSV5hXGPMHxSnBnJWE9Ozhfm7qkjHSnxRPYjzgTDQEPy5OaEMowbg7LX5_XefRBeknaQFJq5GfwG4zpGmbkYkuTcapTVqZAPngEqiEpnWRFsUfxiJ5LY2NCV19vyyN1asCjdyt0TKZG0AxBYjxrlZ655OLJr5Gl24G5Eb0OYy01ODBarAJXUN-Adz6PWKcPaZsMnd1-R7sr22B-LR4NMo5wrP7_ay4ev_u2_nH8uLLh0_nby9K1bRtKlldN7Qfe4wp5wPtaqjbFqtaK5DD0OpB9yNlrOuY7nlHO6X5kGmqoWVtXvVZ8fLYm6f-uUJMYjFRwTznj3JrFITVnPc9o01G6RFVwcUYYBQ-mEWGTRAsdlXiIHZVYlclMBdZRA69uO9fhwX0v8hfNxl4cwQgT3ljIIioDNj8wyZkC0I787_-PyJzqfM</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Kleszczyński, Konrad</creator><creator>Ernst, Insa M.A.</creator><creator>Wagner, Anika E.</creator><creator>Kruse, Nathalie</creator><creator>Zillikens, Detlef</creator><creator>Rimbach, Gerald</creator><creator>Fischer, Tobias W.</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20131201</creationdate><title>Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes</title><author>Kleszczyński, Konrad ; Ernst, Insa M.A. ; Wagner, Anika E. ; Kruse, Nathalie ; Zillikens, Detlef ; Rimbach, Gerald ; Fischer, Tobias W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-633428f800299b273e3550c3dceabb5dbd8f266776d89727cd9bf802de5655653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Anticarcinogenic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Caspase 3 - metabolism</topic><topic>Catalase - metabolism</topic><topic>Cell Line</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>Humans</topic><topic>Isothiocyanates - pharmacology</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nrf2</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - radiation effects</topic><topic>Phenylethyl isothiocyanate</topic><topic>Skin</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Skin - radiation effects</topic><topic>Sulforaphane</topic><topic>Ultraviolet Rays</topic><topic>UVR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kleszczyński, Konrad</creatorcontrib><creatorcontrib>Ernst, Insa M.A.</creatorcontrib><creatorcontrib>Wagner, Anika E.</creatorcontrib><creatorcontrib>Kruse, Nathalie</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><creatorcontrib>Rimbach, Gerald</creatorcontrib><creatorcontrib>Fischer, Tobias W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Pharmacological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kleszczyński, Konrad</au><au>Ernst, Insa M.A.</au><au>Wagner, Anika E.</au><au>Kruse, Nathalie</au><au>Zillikens, Detlef</au><au>Rimbach, Gerald</au><au>Fischer, Tobias W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes</atitle><jtitle>Pharmacological research</jtitle><addtitle>Pharmacol Res</addtitle><date>2013-12-01</date><risdate>2013</risdate><volume>78</volume><spage>28</spage><epage>40</epage><pages>28-40</pages><issn>1043-6618</issn><eissn>1096-1186</eissn><abstract>Chronic UVR-exposure may impair the stress response and antioxidant defense mechanisms of human skin. The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced oxidative stress and apoptosis in ex vivo human full-thickness skin combined with in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction of genes coding for Nrf2-dependent phase II antioxidative enzymes (γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes. Comparative investigations in human ex vivo skin were conducted for analysis of gene expression of above mentioned phase II enzymes and catalase (CAT) as well as hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR exposure of human skin (300mJ/cm2) resulted in a significant time-dependent increase of the number of sunburn cells and caspase-3 activation as biomarkers of apoptosis for up to 48h (p<0.001) and induced a significant decrease of the antioxidant enzyme catalase (p<0.001). This was significantly counteracted by the pre-treatment of human skin with SFN and PEITC (5μM and 10μM). Mechanistic cell culture studies revealed SFN and PEITC to increase Nrf2 activity and Nrf2-dependent gene expression (γGCS, HO-1, NQO1); this was paralleled in human full skin mRNA. In conclusion, the induction of Nrf2-dependent antioxidant pathways seems to be a potential mechanism by which SFN and PEITC protect against UVR-induced oxidative stress and apoptosis in human skin.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>24121007</pmid><doi>10.1016/j.phrs.2013.09.009</doi><tpages>13</tpages></addata></record> |
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| subjects | Anticarcinogenic Agents - pharmacology Apoptosis Apoptosis - drug effects Apoptosis - radiation effects Caspase 3 - metabolism Catalase - metabolism Cell Line Gene Expression Regulation - drug effects Gene Expression Regulation - radiation effects Humans Isothiocyanates - pharmacology NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Nrf2 Oxidative stress Oxidative Stress - drug effects Oxidative Stress - radiation effects Phenylethyl isothiocyanate Skin Skin - drug effects Skin - metabolism Skin - pathology Skin - radiation effects Sulforaphane Ultraviolet Rays UVR |
| title | Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes |
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