Ultraviolet a Radiation Induces Immediate Release of Iron in Human Primary Skin Fibroblasts: The Role of Ferritin
In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1999-06, Vol.96 (12), p.6751-6756 |
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description | In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to skin via generation of reactive oxygen species. We report here that the exposure of human primary skin fibroblasts, FEK4, to UVA radiation causes an immediate release of "free" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UVA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful "free" iron to the cytosol might be a major factor in UVA-induced damage to the skin. |
doi_str_mv | 10.1073/pnas.96.12.6751 |
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This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to skin via generation of reactive oxygen species. We report here that the exposure of human primary skin fibroblasts, FEK4, to UVA radiation causes an immediate release of "free" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UVA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful "free" iron to the cytosol might be a major factor in UVA-induced damage to the skin.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.96.12.6751</identifier><identifier>PMID: 10359784</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>B lymphocytes ; Biological Sciences ; Cells, Cultured ; Cellular biology ; Cytosol ; Delta cells ; Dosage ; Ferritins - metabolism ; Fibroblasts ; Fibroblasts - diagnostic imaging ; Fibroblasts - metabolism ; Humans ; Iron ; Iron - metabolism ; Iron Regulatory Protein 1 ; Iron-Regulatory Proteins ; Iron-Sulfur Proteins - metabolism ; Irradiation ; Oxygen ; Protease inhibitors ; Proteins ; Radiation damage ; Radiation dosage ; Radionuclide Imaging ; RNA-Binding Proteins - metabolism ; Skin - metabolism ; Skin - radiation effects ; Ultraviolet radiation ; Ultraviolet Rays</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1999-06, Vol.96 (12), p.6751-6756</ispartof><rights>Copyright 1933-1999 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 8, 1999</rights><rights>Copyright © 1999, The National Academy of Sciences 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-9a41be67f264b99b469e399a97ed7140a8f989925c696b301103576ffe2ef0fa3</citedby><cites>FETCH-LOGICAL-c585t-9a41be67f264b99b469e399a97ed7140a8f989925c696b301103576ffe2ef0fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/96/12.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/47953$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/47953$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10359784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pourzand, Charareh</creatorcontrib><creatorcontrib>Watkin, Richard D.</creatorcontrib><creatorcontrib>Brown, Jonathan E.</creatorcontrib><creatorcontrib>Tyrrell, Rex M.</creatorcontrib><title>Ultraviolet a Radiation Induces Immediate Release of Iron in Human Primary Skin Fibroblasts: The Role of Ferritin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to skin via generation of reactive oxygen species. We report here that the exposure of human primary skin fibroblasts, FEK4, to UVA radiation causes an immediate release of "free" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UVA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful "free" iron to the cytosol might be a major factor in UVA-induced damage to the skin.</description><subject>B lymphocytes</subject><subject>Biological Sciences</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cytosol</subject><subject>Delta cells</subject><subject>Dosage</subject><subject>Ferritins - metabolism</subject><subject>Fibroblasts</subject><subject>Fibroblasts - diagnostic imaging</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Iron</subject><subject>Iron - metabolism</subject><subject>Iron Regulatory Protein 1</subject><subject>Iron-Regulatory Proteins</subject><subject>Iron-Sulfur Proteins - metabolism</subject><subject>Irradiation</subject><subject>Oxygen</subject><subject>Protease inhibitors</subject><subject>Proteins</subject><subject>Radiation damage</subject><subject>Radiation dosage</subject><subject>Radionuclide Imaging</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Ultraviolet radiation</subject><subject>Ultraviolet Rays</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhSMEokvhjMQBWRzglK3tOHYGcUEVS1eqBCrt2XKyY-olG29tp4J_j6OUassBTpZmvvc0z68oXjK6ZFRVJ_vBxCXIJeNLqWr2qFgwCqyUAujjYkEpV2UjuDgqnsW4pZRC3dCnxRGjVQ2qEYvi5qpPwdw632MihlyYjTPJ-YGsh83YYSTr3Q6nGZIL7NFEJN6SdciEG8jZuDMD-RrczoRf5NuPPFq5Nvi2NzHF9-TyOsuy9aRZYQguueF58cSaPuKLu_e4uFp9ujw9K8-_fF6ffjwvu7qpUwlGsBalslyKFqAVErACMKBwo5igprHQAPC6kyDbirIpk5LWIkdLramOiw-z735sc4QOhxy01_v5WO2N0w83g7vW3_2t5gwaleVv7-TB34wYk9652GHfmwH9GLWEhrGKwX9BprisadNk8M1f4NaPYch_oDlllRC85hk6maEu-BgD2vuDGdVT5XqqXIPUjOup8qx4fZjzgJ87PgAm5Z_1A4d3_wS0Hfs-4c-UyVczuY3Jh3tUKKir6jdJAckj</recordid><startdate>19990608</startdate><enddate>19990608</enddate><creator>Pourzand, Charareh</creator><creator>Watkin, Richard D.</creator><creator>Brown, Jonathan E.</creator><creator>Tyrrell, Rex M.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7U7</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990608</creationdate><title>Ultraviolet a Radiation Induces Immediate Release of Iron in Human Primary Skin Fibroblasts: The Role of Ferritin</title><author>Pourzand, Charareh ; Watkin, Richard D. ; Brown, Jonathan E. ; Tyrrell, Rex M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-9a41be67f264b99b469e399a97ed7140a8f989925c696b301103576ffe2ef0fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>B lymphocytes</topic><topic>Biological Sciences</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Cytosol</topic><topic>Delta cells</topic><topic>Dosage</topic><topic>Ferritins - metabolism</topic><topic>Fibroblasts</topic><topic>Fibroblasts - diagnostic imaging</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Iron</topic><topic>Iron - metabolism</topic><topic>Iron Regulatory Protein 1</topic><topic>Iron-Regulatory Proteins</topic><topic>Iron-Sulfur Proteins - metabolism</topic><topic>Irradiation</topic><topic>Oxygen</topic><topic>Protease inhibitors</topic><topic>Proteins</topic><topic>Radiation damage</topic><topic>Radiation dosage</topic><topic>Radionuclide Imaging</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Ultraviolet radiation</topic><topic>Ultraviolet Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pourzand, Charareh</creatorcontrib><creatorcontrib>Watkin, Richard D.</creatorcontrib><creatorcontrib>Brown, Jonathan E.</creatorcontrib><creatorcontrib>Tyrrell, Rex M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Toxicology Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pourzand, Charareh</au><au>Watkin, Richard D.</au><au>Brown, Jonathan E.</au><au>Tyrrell, Rex M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultraviolet a Radiation Induces Immediate Release of Iron in Human Primary Skin Fibroblasts: The Role of Ferritin</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1999-06-08</date><risdate>1999</risdate><volume>96</volume><issue>12</issue><spage>6751</spage><epage>6756</epage><pages>6751-6756</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>In mammalian cells, the level of the iron-storage protein ferritin (Ft) is tightly controlled by the iron-regulatory protein-1 (IRP-1) at the posttranscriptional level. This regulation prevents iron acting as a catalyst in reactions between reactive oxygen species and biomolecules. The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to skin via generation of reactive oxygen species. We report here that the exposure of human primary skin fibroblasts, FEK4, to UVA radiation causes an immediate release of "free" iron in the cells via proteolysis of Ft. Within minutes of exposure to a range of doses of UVA at natural exposure levels, the binding activity of IRP-1, as well as Ft levels, decreases in a dose-dependent manner. This decrease coincides with a significant leakage of the lysosomal components into the cytosol. Stabilization of Ft molecules occurs only when cells are pretreated with lysosomal protease inhibitors after UVA treatment. We propose that the oxidative damage to lysosomes that leads to Ft degradation and the consequent rapid release of potentially harmful "free" iron to the cytosol might be a major factor in UVA-induced damage to the skin.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>10359784</pmid><doi>10.1073/pnas.96.12.6751</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | B lymphocytes Biological Sciences Cells, Cultured Cellular biology Cytosol Delta cells Dosage Ferritins - metabolism Fibroblasts Fibroblasts - diagnostic imaging Fibroblasts - metabolism Humans Iron Iron - metabolism Iron Regulatory Protein 1 Iron-Regulatory Proteins Iron-Sulfur Proteins - metabolism Irradiation Oxygen Protease inhibitors Proteins Radiation damage Radiation dosage Radionuclide Imaging RNA-Binding Proteins - metabolism Skin - metabolism Skin - radiation effects Ultraviolet radiation Ultraviolet Rays |
title | Ultraviolet a Radiation Induces Immediate Release of Iron in Human Primary Skin Fibroblasts: The Role of Ferritin |
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