Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments
Objective Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondroc...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2016-01, Vol.68 (1), p.117-126 |
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| creator | Wood, Scott T. Long, David L. Reisz, Julie A. Yammani, Raghunatha R. Burke, Elizabeth A. Klomsiri, Chananat Poole, Leslie B. Furdui, Cristina M. Loeser, Richard F. |
| description | Objective
Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated in normal chondrocytes as a mechanism by which fragments of fibronectin (FN‐f) stimulate chondrocyte catabolic signaling.
Methods
Chondrocytes isolated from OA and normal human articular cartilage were analyzed using analogs of dimedone that specifically and irreversibly react with protein S‐sulfenylated cysteines. Global S‐sulfenylation was measured in cell lysates with and without FN‐f stimulation by immunoblotting and in fixed cells by confocal microscopy. S‐sulfenylation in specific proteins was identified by mass spectroscopy and confirmed by immunoblotting. Src activity was measured in live cells using a fluorescence resonance energy transfer biosensor.
Results
Proteins in chondrocytes isolated from OA cartilage were found to have elevated basal levels of S‐sulfenylation relative to those of chondrocytes from normal cartilage. Treatment of normal chondrocytes with FN‐f induced increased levels of S‐sulfenylation in multiple proteins, including the tyrosine kinase Src. FN‐f treatment also increased the levels of Src activity. Pretreatment with dimedone to alter S‐sulfenylation function or with Src kinase inhibitors inhibited FN‐f–induced production of matrix metalloproteinase 13.
Conclusion
These results demonstrate for the first time the presence of oxidative posttranslational modification of proteins in human articular chondrocytes by S‐sulfenylation. Due to the ability to regulate the activity of a number of cell signaling pathways, including catabolic mediators induced by fibronectin fragments, S‐sulfenylation may contribute to cartilage destruction in OA and warrants further investigation. |
| doi_str_mv | 10.1002/art.39326 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4849859</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1780515731</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4766-82e312c5685e8f80b57a2a88dddace7d69577ca6216e34f62f70cdd98e7671853</originalsourceid><addsrcrecordid>eNqNkc9qFTEUhwdRbKld-AIy4EYXt00yk38boQxeFSpCW3EZcpMzc1NmkppkqnfnI_iMPomp0xYVBLPICeTLL8n5quopRkcYIXKsYz5qZEPYg2qflLKiBNGHd2ss8V51mNIlKkNyxBB9XO0R1uCWELFfjd0uZXAefnz7_h6s0xlsfQY2fC3zMI86u-Dr0NcdjGN97gavR-eH2vm62wZvYzC7DKk-z266ocvpTy5v67XbxODB5AKuox4m8Dk9qR71ekxweFsPqo_r1xfd29XphzfvupPTlWk5YytBoMHEUCYoiF6gDeWaaCGstdoAt0xSzo1mBDNo2p6RniNjrRTAGceCNgfVqyX3at5MYE25O-pRXUU36bhTQTv15453WzWEa9WKVgoqS8CL24AYPs-QsppcMqUD2kOYk8JcIIopb_B_oMWBpLRpC_r8L_QyzLE0dKEaJhFBhXq5UCaGlCL09-_GSN0YV8W4-mW8sM9-_-g9eee3AMcL8MWNsPt3kjo5u1gifwIdl7bX</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1751369020</pqid></control><display><type>article</type><title>Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Wood, Scott T. ; Long, David L. ; Reisz, Julie A. ; Yammani, Raghunatha R. ; Burke, Elizabeth A. ; Klomsiri, Chananat ; Poole, Leslie B. ; Furdui, Cristina M. ; Loeser, Richard F.</creator><creatorcontrib>Wood, Scott T. ; Long, David L. ; Reisz, Julie A. ; Yammani, Raghunatha R. ; Burke, Elizabeth A. ; Klomsiri, Chananat ; Poole, Leslie B. ; Furdui, Cristina M. ; Loeser, Richard F.</creatorcontrib><description>Objective
Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated in normal chondrocytes as a mechanism by which fragments of fibronectin (FN‐f) stimulate chondrocyte catabolic signaling.
Methods
Chondrocytes isolated from OA and normal human articular cartilage were analyzed using analogs of dimedone that specifically and irreversibly react with protein S‐sulfenylated cysteines. Global S‐sulfenylation was measured in cell lysates with and without FN‐f stimulation by immunoblotting and in fixed cells by confocal microscopy. S‐sulfenylation in specific proteins was identified by mass spectroscopy and confirmed by immunoblotting. Src activity was measured in live cells using a fluorescence resonance energy transfer biosensor.
Results
Proteins in chondrocytes isolated from OA cartilage were found to have elevated basal levels of S‐sulfenylation relative to those of chondrocytes from normal cartilage. Treatment of normal chondrocytes with FN‐f induced increased levels of S‐sulfenylation in multiple proteins, including the tyrosine kinase Src. FN‐f treatment also increased the levels of Src activity. Pretreatment with dimedone to alter S‐sulfenylation function or with Src kinase inhibitors inhibited FN‐f–induced production of matrix metalloproteinase 13.
Conclusion
These results demonstrate for the first time the presence of oxidative posttranslational modification of proteins in human articular chondrocytes by S‐sulfenylation. Due to the ability to regulate the activity of a number of cell signaling pathways, including catabolic mediators induced by fibronectin fragments, S‐sulfenylation may contribute to cartilage destruction in OA and warrants further investigation.</description><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.39326</identifier><identifier>PMID: 26314228</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Cartilage, Articular - cytology ; Case-Control Studies ; Chondrocytes - drug effects ; Chondrocytes - metabolism ; Cyclohexanones - pharmacology ; Cysteine - metabolism ; Female ; Fibronectins - pharmacology ; History, Ancient ; Humans ; Immunoblotting ; Mass Spectrometry ; Matrix Metalloproteinase 13 - drug effects ; Matrix Metalloproteinase 13 - metabolism ; Microscopy, Confocal ; Middle Aged ; Osteoarthritis - metabolism ; Oxidation-Reduction ; Peptide Fragments - pharmacology ; Protein Processing, Post-Translational ; Proteins ; Signal Transduction ; src-Family Kinases - drug effects ; src-Family Kinases - metabolism ; Sulfenic Acids - metabolism</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2016-01, Vol.68 (1), p.117-126</ispartof><rights>2016, American College of Rheumatology</rights><rights>2016, American College of Rheumatology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4766-82e312c5685e8f80b57a2a88dddace7d69577ca6216e34f62f70cdd98e7671853</citedby><cites>FETCH-LOGICAL-c4766-82e312c5685e8f80b57a2a88dddace7d69577ca6216e34f62f70cdd98e7671853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.39326$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.39326$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26314228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wood, Scott T.</creatorcontrib><creatorcontrib>Long, David L.</creatorcontrib><creatorcontrib>Reisz, Julie A.</creatorcontrib><creatorcontrib>Yammani, Raghunatha R.</creatorcontrib><creatorcontrib>Burke, Elizabeth A.</creatorcontrib><creatorcontrib>Klomsiri, Chananat</creatorcontrib><creatorcontrib>Poole, Leslie B.</creatorcontrib><creatorcontrib>Furdui, Cristina M.</creatorcontrib><creatorcontrib>Loeser, Richard F.</creatorcontrib><title>Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheumatol</addtitle><description>Objective
Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated in normal chondrocytes as a mechanism by which fragments of fibronectin (FN‐f) stimulate chondrocyte catabolic signaling.
Methods
Chondrocytes isolated from OA and normal human articular cartilage were analyzed using analogs of dimedone that specifically and irreversibly react with protein S‐sulfenylated cysteines. Global S‐sulfenylation was measured in cell lysates with and without FN‐f stimulation by immunoblotting and in fixed cells by confocal microscopy. S‐sulfenylation in specific proteins was identified by mass spectroscopy and confirmed by immunoblotting. Src activity was measured in live cells using a fluorescence resonance energy transfer biosensor.
Results
Proteins in chondrocytes isolated from OA cartilage were found to have elevated basal levels of S‐sulfenylation relative to those of chondrocytes from normal cartilage. Treatment of normal chondrocytes with FN‐f induced increased levels of S‐sulfenylation in multiple proteins, including the tyrosine kinase Src. FN‐f treatment also increased the levels of Src activity. Pretreatment with dimedone to alter S‐sulfenylation function or with Src kinase inhibitors inhibited FN‐f–induced production of matrix metalloproteinase 13.
Conclusion
These results demonstrate for the first time the presence of oxidative posttranslational modification of proteins in human articular chondrocytes by S‐sulfenylation. Due to the ability to regulate the activity of a number of cell signaling pathways, including catabolic mediators induced by fibronectin fragments, S‐sulfenylation may contribute to cartilage destruction in OA and warrants further investigation.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cartilage, Articular - cytology</subject><subject>Case-Control Studies</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - metabolism</subject><subject>Cyclohexanones - pharmacology</subject><subject>Cysteine - metabolism</subject><subject>Female</subject><subject>Fibronectins - pharmacology</subject><subject>History, Ancient</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Mass Spectrometry</subject><subject>Matrix Metalloproteinase 13 - drug effects</subject><subject>Matrix Metalloproteinase 13 - metabolism</subject><subject>Microscopy, Confocal</subject><subject>Middle Aged</subject><subject>Osteoarthritis - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Peptide Fragments - pharmacology</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>src-Family Kinases - drug effects</subject><subject>src-Family Kinases - metabolism</subject><subject>Sulfenic Acids - metabolism</subject><issn>2326-5191</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9qFTEUhwdRbKld-AIy4EYXt00yk38boQxeFSpCW3EZcpMzc1NmkppkqnfnI_iMPomp0xYVBLPICeTLL8n5quopRkcYIXKsYz5qZEPYg2qflLKiBNGHd2ss8V51mNIlKkNyxBB9XO0R1uCWELFfjd0uZXAefnz7_h6s0xlsfQY2fC3zMI86u-Dr0NcdjGN97gavR-eH2vm62wZvYzC7DKk-z266ocvpTy5v67XbxODB5AKuox4m8Dk9qR71ekxweFsPqo_r1xfd29XphzfvupPTlWk5YytBoMHEUCYoiF6gDeWaaCGstdoAt0xSzo1mBDNo2p6RniNjrRTAGceCNgfVqyX3at5MYE25O-pRXUU36bhTQTv15453WzWEa9WKVgoqS8CL24AYPs-QsppcMqUD2kOYk8JcIIopb_B_oMWBpLRpC_r8L_QyzLE0dKEaJhFBhXq5UCaGlCL09-_GSN0YV8W4-mW8sM9-_-g9eee3AMcL8MWNsPt3kjo5u1gifwIdl7bX</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Wood, Scott T.</creator><creator>Long, David L.</creator><creator>Reisz, Julie A.</creator><creator>Yammani, Raghunatha R.</creator><creator>Burke, Elizabeth A.</creator><creator>Klomsiri, Chananat</creator><creator>Poole, Leslie B.</creator><creator>Furdui, Cristina M.</creator><creator>Loeser, Richard F.</creator><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201601</creationdate><title>Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments</title><author>Wood, Scott T. ; Long, David L. ; Reisz, Julie A. ; Yammani, Raghunatha R. ; Burke, Elizabeth A. ; Klomsiri, Chananat ; Poole, Leslie B. ; Furdui, Cristina M. ; Loeser, Richard F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4766-82e312c5685e8f80b57a2a88dddace7d69577ca6216e34f62f70cdd98e7671853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cartilage, Articular - cytology</topic><topic>Case-Control Studies</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - metabolism</topic><topic>Cyclohexanones - pharmacology</topic><topic>Cysteine - metabolism</topic><topic>Female</topic><topic>Fibronectins - pharmacology</topic><topic>History, Ancient</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Mass Spectrometry</topic><topic>Matrix Metalloproteinase 13 - drug effects</topic><topic>Matrix Metalloproteinase 13 - metabolism</topic><topic>Microscopy, Confocal</topic><topic>Middle Aged</topic><topic>Osteoarthritis - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Peptide Fragments - pharmacology</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Signal Transduction</topic><topic>src-Family Kinases - drug effects</topic><topic>src-Family Kinases - metabolism</topic><topic>Sulfenic Acids - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wood, Scott T.</creatorcontrib><creatorcontrib>Long, David L.</creatorcontrib><creatorcontrib>Reisz, Julie A.</creatorcontrib><creatorcontrib>Yammani, Raghunatha R.</creatorcontrib><creatorcontrib>Burke, Elizabeth A.</creatorcontrib><creatorcontrib>Klomsiri, Chananat</creatorcontrib><creatorcontrib>Poole, Leslie B.</creatorcontrib><creatorcontrib>Furdui, Cristina M.</creatorcontrib><creatorcontrib>Loeser, Richard F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wood, Scott T.</au><au>Long, David L.</au><au>Reisz, Julie A.</au><au>Yammani, Raghunatha R.</au><au>Burke, Elizabeth A.</au><au>Klomsiri, Chananat</au><au>Poole, Leslie B.</au><au>Furdui, Cristina M.</au><au>Loeser, Richard F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheumatol</addtitle><date>2016-01</date><risdate>2016</risdate><volume>68</volume><issue>1</issue><spage>117</spage><epage>126</epage><pages>117-126</pages><issn>2326-5191</issn><eissn>2326-5205</eissn><abstract>Objective
Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated in normal chondrocytes as a mechanism by which fragments of fibronectin (FN‐f) stimulate chondrocyte catabolic signaling.
Methods
Chondrocytes isolated from OA and normal human articular cartilage were analyzed using analogs of dimedone that specifically and irreversibly react with protein S‐sulfenylated cysteines. Global S‐sulfenylation was measured in cell lysates with and without FN‐f stimulation by immunoblotting and in fixed cells by confocal microscopy. S‐sulfenylation in specific proteins was identified by mass spectroscopy and confirmed by immunoblotting. Src activity was measured in live cells using a fluorescence resonance energy transfer biosensor.
Results
Proteins in chondrocytes isolated from OA cartilage were found to have elevated basal levels of S‐sulfenylation relative to those of chondrocytes from normal cartilage. Treatment of normal chondrocytes with FN‐f induced increased levels of S‐sulfenylation in multiple proteins, including the tyrosine kinase Src. FN‐f treatment also increased the levels of Src activity. Pretreatment with dimedone to alter S‐sulfenylation function or with Src kinase inhibitors inhibited FN‐f–induced production of matrix metalloproteinase 13.
Conclusion
These results demonstrate for the first time the presence of oxidative posttranslational modification of proteins in human articular chondrocytes by S‐sulfenylation. Due to the ability to regulate the activity of a number of cell signaling pathways, including catabolic mediators induced by fibronectin fragments, S‐sulfenylation may contribute to cartilage destruction in OA and warrants further investigation.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26314228</pmid><doi>10.1002/art.39326</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Cartilage, Articular - cytology Case-Control Studies Chondrocytes - drug effects Chondrocytes - metabolism Cyclohexanones - pharmacology Cysteine - metabolism Female Fibronectins - pharmacology History, Ancient Humans Immunoblotting Mass Spectrometry Matrix Metalloproteinase 13 - drug effects Matrix Metalloproteinase 13 - metabolism Microscopy, Confocal Middle Aged Osteoarthritis - metabolism Oxidation-Reduction Peptide Fragments - pharmacology Protein Processing, Post-Translational Proteins Signal Transduction src-Family Kinases - drug effects src-Family Kinases - metabolism Sulfenic Acids - metabolism |
| title | Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments |
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