Superoxide targets calcineurin signaling in vascular endothelium
Superoxide emerges as key regulatory molecule in many aspects of vascular physiology and disease, but identification of superoxide targets in the vasculature remains elusive. In this work, we investigated the possibility of inhibition of protein phosphatase calcineurin by superoxide in endothelial c...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2005-09, Vol.334 (4), p.1061-1067 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Namgaladze, Dmitry Shcherbyna, Ivanna Kienhöfer, Joachim Hofer, H. Werner Ullrich, Volker |
| description | Superoxide emerges as key regulatory molecule in many aspects of vascular physiology and disease, but identification of superoxide targets in the vasculature remains elusive. In this work, we investigated the possibility of inhibition of protein phosphatase calcineurin by superoxide in endothelial cells. We employed a redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) to generate superoxide inside the cells. DMNQ caused inhibition of cellular calcineurin phosphatase activity, which was reversible upon DMNQ removal. Inhibition was suppressed by pre-incubating the cells with copper/zinc superoxide dismutase (Cu,ZnSOD). In addition, reducing cellular Cu,ZnSOD activity by diethylthiocarbamic acid treatment resulted in calcineurin inhibition and enhanced sensitivity to DMNQ. Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature. |
| doi_str_mv | 10.1016/j.bbrc.2005.07.003 |
| format | Article |
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Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2005.07.003</identifier><identifier>PMID: 16038879</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; Calcineurin ; Calcineurin - metabolism ; CALMODULIN ; Cattle ; Cells, Cultured ; COPPER ; Dose-Response Relationship, Drug ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; ENDOTHELIUM ; GENE REGULATION ; Humans ; INHIBITION ; Naphthoquinones - administration & dosage ; NFAT ; Oxidative stress ; PHYSIOLOGY ; Protein phosphatase ; Redox regulation ; SENSITIVITY ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Superoxide ; SUPEROXIDE DISMUTASE ; Superoxide Dismutase - metabolism ; Superoxides - metabolism ; TIRON ; TRANSCRIPTION FACTORS ; TRANSLOCATION ; Vascular disease ; VASCULAR DISEASES ; ZINC</subject><ispartof>Biochemical and biophysical research communications, 2005-09, Vol.334 (4), p.1061-1067</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-c06f261a1ea3ada05905390657c4fa310c4e5ce3438636c66f65a80f7868dab03</citedby><cites>FETCH-LOGICAL-c413t-c06f261a1ea3ada05905390657c4fa310c4e5ce3438636c66f65a80f7868dab03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2005.07.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,778,782,883,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16038879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/20710954$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Namgaladze, Dmitry</creatorcontrib><creatorcontrib>Shcherbyna, Ivanna</creatorcontrib><creatorcontrib>Kienhöfer, Joachim</creatorcontrib><creatorcontrib>Hofer, H. Werner</creatorcontrib><creatorcontrib>Ullrich, Volker</creatorcontrib><title>Superoxide targets calcineurin signaling in vascular endothelium</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Superoxide emerges as key regulatory molecule in many aspects of vascular physiology and disease, but identification of superoxide targets in the vasculature remains elusive. In this work, we investigated the possibility of inhibition of protein phosphatase calcineurin by superoxide in endothelial cells. We employed a redox cycler 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) to generate superoxide inside the cells. DMNQ caused inhibition of cellular calcineurin phosphatase activity, which was reversible upon DMNQ removal. Inhibition was suppressed by pre-incubating the cells with copper/zinc superoxide dismutase (Cu,ZnSOD). In addition, reducing cellular Cu,ZnSOD activity by diethylthiocarbamic acid treatment resulted in calcineurin inhibition and enhanced sensitivity to DMNQ. Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>Calcineurin</subject><subject>Calcineurin - metabolism</subject><subject>CALMODULIN</subject><subject>Cattle</subject><subject>Cells, Cultured</subject><subject>COPPER</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>ENDOTHELIUM</subject><subject>GENE REGULATION</subject><subject>Humans</subject><subject>INHIBITION</subject><subject>Naphthoquinones - administration & dosage</subject><subject>NFAT</subject><subject>Oxidative stress</subject><subject>PHYSIOLOGY</subject><subject>Protein phosphatase</subject><subject>Redox regulation</subject><subject>SENSITIVITY</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Superoxide</subject><subject>SUPEROXIDE DISMUTASE</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxides - metabolism</subject><subject>TIRON</subject><subject>TRANSCRIPTION FACTORS</subject><subject>TRANSLOCATION</subject><subject>Vascular disease</subject><subject>VASCULAR DISEASES</subject><subject>ZINC</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9r20AQxZfSUDtuv0APRVDoTcqsVruSIIcU0_wBQw5pobdlPRrZa-SVsyuZ5tt3hQ25Jadh4PcevPcY-8oh48DV1S5brz1mOYDMoMwAxAc251BDmnMoPrI5AKg0r_nfGbsMYQfAeaHqT2zGFYiqKus5u3kaD-T7f7ahZDB-Q0NI0HRoHY3euiTYjTOddZskPkcTcOyMT8g1_bClzo77z-yiNV2gL-e7YH9uf_1e3qerx7uH5c9VigUXQ4qg2lxxw8kI0xiQNUhRg5IlFq0RHLAgiSQKUSmhUKlWSVNBW1aqaswaxIJ9P_n2YbA6oB0It9g7RzjoHMqYWxaR-nGiDr5_HikMem8DUtcZR_0YtKoKIWI774K8lLLORR3B_ASi70Pw1OqDt3vjXzQHPc2gd3qaQU8zaCh1nCGKvp3dx_WemlfJufcIXJ8AipUdLfkpETmkxvopUNPbt_z_AyPbl94</recordid><startdate>20050909</startdate><enddate>20050909</enddate><creator>Namgaladze, Dmitry</creator><creator>Shcherbyna, Ivanna</creator><creator>Kienhöfer, Joachim</creator><creator>Hofer, H. 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Werner ; Ullrich, Volker</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-c06f261a1ea3ada05905390657c4fa310c4e5ce3438636c66f65a80f7868dab03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>Calcineurin</topic><topic>Calcineurin - metabolism</topic><topic>CALMODULIN</topic><topic>Cattle</topic><topic>Cells, Cultured</topic><topic>COPPER</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>ENDOTHELIUM</topic><topic>GENE REGULATION</topic><topic>Humans</topic><topic>INHIBITION</topic><topic>Naphthoquinones - administration & dosage</topic><topic>NFAT</topic><topic>Oxidative stress</topic><topic>PHYSIOLOGY</topic><topic>Protein phosphatase</topic><topic>Redox regulation</topic><topic>SENSITIVITY</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Superoxide</topic><topic>SUPEROXIDE DISMUTASE</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxides - metabolism</topic><topic>TIRON</topic><topic>TRANSCRIPTION FACTORS</topic><topic>TRANSLOCATION</topic><topic>Vascular disease</topic><topic>VASCULAR DISEASES</topic><topic>ZINC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Namgaladze, Dmitry</creatorcontrib><creatorcontrib>Shcherbyna, Ivanna</creatorcontrib><creatorcontrib>Kienhöfer, Joachim</creatorcontrib><creatorcontrib>Hofer, H. 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DMNQ caused inhibition of cellular calcineurin phosphatase activity, which was reversible upon DMNQ removal. Inhibition was suppressed by pre-incubating the cells with copper/zinc superoxide dismutase (Cu,ZnSOD). In addition, reducing cellular Cu,ZnSOD activity by diethylthiocarbamic acid treatment resulted in calcineurin inhibition and enhanced sensitivity to DMNQ. Further, we could show that DMNQ inhibits calcineurin-dependent nuclear translocation and transcriptional activation of NFAT transcription factor, and Cu,ZnSOD or superoxide scavenger Tiron reduced the inhibition. Thus, superoxide generation in endothelial cells results in inhibition of calcineurin signaling, which could have important pathophysiological implications in the vasculature.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16038879</pmid><doi>10.1016/j.bbrc.2005.07.003</doi><tpages>7</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Animals Calcineurin Calcineurin - metabolism CALMODULIN Cattle Cells, Cultured COPPER Dose-Response Relationship, Drug Endothelial Cells - drug effects Endothelial Cells - metabolism ENDOTHELIUM GENE REGULATION Humans INHIBITION Naphthoquinones - administration & dosage NFAT Oxidative stress PHYSIOLOGY Protein phosphatase Redox regulation SENSITIVITY Signal Transduction - drug effects Signal Transduction - physiology Superoxide SUPEROXIDE DISMUTASE Superoxide Dismutase - metabolism Superoxides - metabolism TIRON TRANSCRIPTION FACTORS TRANSLOCATION Vascular disease VASCULAR DISEASES ZINC |
| title | Superoxide targets calcineurin signaling in vascular endothelium |
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