Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin
UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR‐mediated photodamage and induce the DNA‐base‐oxidized, intermediate 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG). Herein, we re...
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| Veröffentlicht in: | Journal of pineal research 2013-04, Vol.54 (3), p.303-312 |
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| creator | Fischer, Tobias W. Kleszczyński, Konrad Hardkop, Lena H. Kruse, Nathalie Zillikens, Detlef |
| description | UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR‐mediated photodamage and induce the DNA‐base‐oxidized, intermediate 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG). Herein, we report the protective action of melatonin against UVR‐induced 8‐OHdG formation and depletion of antioxidative enzymes using ex vivo human full‐thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm2)‐ and time‐dependent manner (0, 24, 48 hr post‐UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8‐OHdG formation were studied by real‐time PCR and immunofluorescence/immunohistochemical staining. UVR‐treated skin revealed significant and immediate (0 hr 300 mJ/cm2) reduction of gene expression, and this effect intensified within 24 hr post‐UVR. Simultaneous increase in 8‐OHdG‐positive keratinocytes occurred already after 0 hr post‐UVR reaching 71% and 99% up‐regulation at 100 and 300 mJ/cm2, respectively (P |
| doi_str_mv | 10.1111/jpi.12018 |
| format | Article |
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Reactive oxygen species are key players in UVR‐mediated photodamage and induce the DNA‐base‐oxidized, intermediate 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG). Herein, we report the protective action of melatonin against UVR‐induced 8‐OHdG formation and depletion of antioxidative enzymes using ex vivo human full‐thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm2)‐ and time‐dependent manner (0, 24, 48 hr post‐UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8‐OHdG formation were studied by real‐time PCR and immunofluorescence/immunohistochemical staining. UVR‐treated skin revealed significant and immediate (0 hr 300 mJ/cm2) reduction of gene expression, and this effect intensified within 24 hr post‐UVR. Simultaneous increase in 8‐OHdG‐positive keratinocytes occurred already after 0 hr post‐UVR reaching 71% and 99% up‐regulation at 100 and 300 mJ/cm2, respectively (P < 0.001). Preincubation with melatonin (10−3 m) led to 32% and 29% significant reductions in 8‐OHdG‐positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR‐induced oxidative damage in human skin.</description><identifier>ISSN: 0742-3098</identifier><identifier>EISSN: 1600-079X</identifier><identifier>DOI: 10.1111/jpi.12018</identifier><identifier>PMID: 23110400</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>8-hydroxy-2'-deoxyguanosine ; Adult ; Analysis of Variance ; Antioxidants - metabolism ; Antioxidants - pharmacology ; catalase ; Catalase - biosynthesis ; Catalase - genetics ; Catalase - metabolism ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; DNA Damage ; glutathione peroxidase ; Glutathione Peroxidase - biosynthesis ; Glutathione Peroxidase - genetics ; Glutathione Peroxidase - metabolism ; human full-thickness skin ; Humans ; Immunohistochemistry ; melatonin ; Melatonin - pharmacology ; Middle Aged ; Organ Culture Techniques ; Real-Time Polymerase Chain Reaction ; Skin - drug effects ; Skin - enzymology ; Skin - metabolism ; Skin - radiation effects ; Skin Physiological Phenomena - drug effects ; superoxide dismutase ; Superoxide Dismutase - biosynthesis ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism ; ultraviolet radiation ; Ultraviolet Rays ; Young Adult</subject><ispartof>Journal of pineal research, 2013-04, Vol.54 (3), p.303-312</ispartof><rights>2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4038-1974050f340dbb435e36ce26296f024f9b5c97636c3c9ef3ea95af42925303fc3</citedby><cites>FETCH-LOGICAL-c4038-1974050f340dbb435e36ce26296f024f9b5c97636c3c9ef3ea95af42925303fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjpi.12018$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjpi.12018$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23110400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fischer, Tobias W.</creatorcontrib><creatorcontrib>Kleszczyński, Konrad</creatorcontrib><creatorcontrib>Hardkop, Lena H.</creatorcontrib><creatorcontrib>Kruse, Nathalie</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><title>Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin</title><title>Journal of pineal research</title><addtitle>J. Pineal Res</addtitle><description>UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR‐mediated photodamage and induce the DNA‐base‐oxidized, intermediate 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG). Herein, we report the protective action of melatonin against UVR‐induced 8‐OHdG formation and depletion of antioxidative enzymes using ex vivo human full‐thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm2)‐ and time‐dependent manner (0, 24, 48 hr post‐UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8‐OHdG formation were studied by real‐time PCR and immunofluorescence/immunohistochemical staining. UVR‐treated skin revealed significant and immediate (0 hr 300 mJ/cm2) reduction of gene expression, and this effect intensified within 24 hr post‐UVR. Simultaneous increase in 8‐OHdG‐positive keratinocytes occurred already after 0 hr post‐UVR reaching 71% and 99% up‐regulation at 100 and 300 mJ/cm2, respectively (P < 0.001). Preincubation with melatonin (10−3 m) led to 32% and 29% significant reductions in 8‐OHdG‐positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR‐induced oxidative damage in human skin.</description><subject>8-hydroxy-2'-deoxyguanosine</subject><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Antioxidants - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>catalase</subject><subject>Catalase - biosynthesis</subject><subject>Catalase - genetics</subject><subject>Catalase - metabolism</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>DNA Damage</subject><subject>glutathione peroxidase</subject><subject>Glutathione Peroxidase - biosynthesis</subject><subject>Glutathione Peroxidase - genetics</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>human full-thickness skin</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>melatonin</subject><subject>Melatonin - pharmacology</subject><subject>Middle Aged</subject><subject>Organ Culture Techniques</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Skin - drug effects</subject><subject>Skin - enzymology</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Skin Physiological Phenomena - drug effects</subject><subject>superoxide dismutase</subject><subject>Superoxide Dismutase - biosynthesis</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>ultraviolet radiation</subject><subject>Ultraviolet Rays</subject><subject>Young Adult</subject><issn>0742-3098</issn><issn>1600-079X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1uEzEURi0EoqGw4AWQdzRS3N4Zz-8yTSEUNWkFLbCznPF14jZjj8aTMOE1eSEcQrvDG19dn-_I0kfI2whOo3DO7htzGsUQFc_IIMoAGOTlj-dkAHkSMw5lcUReeX8PAEVRZC_JUcyjCBKAAfk9w7XsnDWWol1JW6Gn0nbG9UbJzmwxrH_taqRLtGHumxa9N87Sk8n4dkSnN_2Ifr2-GI5oeNmi7TztVmhaevftCzNWbSpUVGGzxuC0o-BWgXQdVoGUS2ms7_YJql1byz1DnaYX8zFVspZLpCcFW-1U6_odi98zhWFYbqR13lgc0v23e7o1W0dXm1pa6h-MfU1eaLn2-ObffUzuPn64nXxiV9fTy8n4ilUJ8IJFZZ5ACponoBaLhKfIswrjLC4zDXGiy0ValXkWlrwqUXOUZSp1EpdxyoHrih-T4cFbtc77FrVoWlPLdiciEPtiRChG_C0msO8ObLNZ1KieyMcmAnB2AH6aNe7-bxKfby4fleyQML7D_ikh2weR5TxPxff5VBSzyfQ8y2dizv8AAVmoxQ</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Fischer, Tobias W.</creator><creator>Kleszczyński, Konrad</creator><creator>Hardkop, Lena H.</creator><creator>Kruse, Nathalie</creator><creator>Zillikens, Detlef</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201304</creationdate><title>Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin</title><author>Fischer, Tobias W. ; Kleszczyński, Konrad ; Hardkop, Lena H. ; Kruse, Nathalie ; Zillikens, Detlef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4038-1974050f340dbb435e36ce26296f024f9b5c97636c3c9ef3ea95af42925303fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>8-hydroxy-2'-deoxyguanosine</topic><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Antioxidants - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>catalase</topic><topic>Catalase - biosynthesis</topic><topic>Catalase - genetics</topic><topic>Catalase - metabolism</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - metabolism</topic><topic>DNA Damage</topic><topic>glutathione peroxidase</topic><topic>Glutathione Peroxidase - biosynthesis</topic><topic>Glutathione Peroxidase - genetics</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>human full-thickness skin</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>melatonin</topic><topic>Melatonin - pharmacology</topic><topic>Middle Aged</topic><topic>Organ Culture Techniques</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Skin - drug effects</topic><topic>Skin - enzymology</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Skin Physiological Phenomena - drug effects</topic><topic>superoxide dismutase</topic><topic>Superoxide Dismutase - biosynthesis</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>ultraviolet radiation</topic><topic>Ultraviolet Rays</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fischer, Tobias W.</creatorcontrib><creatorcontrib>Kleszczyński, Konrad</creatorcontrib><creatorcontrib>Hardkop, Lena H.</creatorcontrib><creatorcontrib>Kruse, Nathalie</creatorcontrib><creatorcontrib>Zillikens, Detlef</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of pineal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fischer, Tobias W.</au><au>Kleszczyński, Konrad</au><au>Hardkop, Lena H.</au><au>Kruse, Nathalie</au><au>Zillikens, Detlef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin</atitle><jtitle>Journal of pineal research</jtitle><addtitle>J. Pineal Res</addtitle><date>2013-04</date><risdate>2013</risdate><volume>54</volume><issue>3</issue><spage>303</spage><epage>312</epage><pages>303-312</pages><issn>0742-3098</issn><eissn>1600-079X</eissn><abstract>UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR‐mediated photodamage and induce the DNA‐base‐oxidized, intermediate 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG). Herein, we report the protective action of melatonin against UVR‐induced 8‐OHdG formation and depletion of antioxidative enzymes using ex vivo human full‐thickness skin exposed to UVR in a dose (0, 100, 300 mJ/cm2)‐ and time‐dependent manner (0, 24, 48 hr post‐UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8‐OHdG formation were studied by real‐time PCR and immunofluorescence/immunohistochemical staining. UVR‐treated skin revealed significant and immediate (0 hr 300 mJ/cm2) reduction of gene expression, and this effect intensified within 24 hr post‐UVR. Simultaneous increase in 8‐OHdG‐positive keratinocytes occurred already after 0 hr post‐UVR reaching 71% and 99% up‐regulation at 100 and 300 mJ/cm2, respectively (P < 0.001). Preincubation with melatonin (10−3 m) led to 32% and 29% significant reductions in 8‐OHdG‐positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR‐induced oxidative damage in human skin.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23110400</pmid><doi>10.1111/jpi.12018</doi><tpages>10</tpages></addata></record> |
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| ispartof | Journal of pineal research, 2013-04, Vol.54 (3), p.303-312 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | 8-hydroxy-2'-deoxyguanosine Adult Analysis of Variance Antioxidants - metabolism Antioxidants - pharmacology catalase Catalase - biosynthesis Catalase - genetics Catalase - metabolism Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism DNA Damage glutathione peroxidase Glutathione Peroxidase - biosynthesis Glutathione Peroxidase - genetics Glutathione Peroxidase - metabolism human full-thickness skin Humans Immunohistochemistry melatonin Melatonin - pharmacology Middle Aged Organ Culture Techniques Real-Time Polymerase Chain Reaction Skin - drug effects Skin - enzymology Skin - metabolism Skin - radiation effects Skin Physiological Phenomena - drug effects superoxide dismutase Superoxide Dismutase - biosynthesis Superoxide Dismutase - genetics Superoxide Dismutase - metabolism ultraviolet radiation Ultraviolet Rays Young Adult |
| title | Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin |
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