Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH...
Gespeichert in:
| Veröffentlicht in: | Biochemical and biophysical research communications 2003-09, Vol.308 (4), p.984-989 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 989 |
|---|---|
| container_issue | 4 |
| container_start_page | 984 |
| container_title | Biochemical and biophysical research communications |
| container_volume | 308 |
| creator | Smith, Caroline L. Birdsey, Graeme M. Anthony, Shelagh Arrigoni, Francesca I. Leiper, James M. Vallance, Patrick |
| description | Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor,
S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1
mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation. |
| doi_str_mv | 10.1016/S0006-291X(03)01507-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73603172</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006291X03015079</els_id><sourcerecordid>18830968</sourcerecordid><originalsourceid>FETCH-LOGICAL-c505t-f4ef82613f0a58dfa079ba7190c07f41eb87d32acfb5789179e090d17be0b40a3</originalsourceid><addsrcrecordid>eNqFkVtv1DAQha0K1C6lP6HITwikpszk5vipWvUGUisegKpvlmNPWEMSBzu7Iv-ebHeBxz6NNPrOXM5h7BThHAHLD18AoExSiY_vIHsPWIBI5AFbIEhIUoT8BVv8Q47Yqxh_ACDmpTxkR5jKVFRYLtjPK9fRuJpaHb673vXE7d9G53q_mmzwrY7EtRndxo0T77xdt3qkyJdX90ve0obaeMYfrm9vOP0eAsXofH_GdW-5obblw4p6P04DvWYvG91GOtnXY_bt5vrr5cfk7vPtp8vlXWIKKMakyamp0hKzBnRR2UaDkLUWKMGAaHKkuhI2S7Vp6kJUEoWk-WeLoiaoc9DZMXu7mzsE_2tNcVSdi9tTdE9-HZXISshQpM-CWFUZyLKawWIHmuBjDNSoIbhOh0khqG0c6ikOtfVaQaae4lBy1r3ZL1jXHdn_qr3_M3CxA2YPaeMoqGgc9YasC2RGZb17ZsUfgcSbww</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18830968</pqid></control><display><type>article</type><title>Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Smith, Caroline L. ; Birdsey, Graeme M. ; Anthony, Shelagh ; Arrigoni, Francesca I. ; Leiper, James M. ; Vallance, Patrick</creator><creatorcontrib>Smith, Caroline L. ; Birdsey, Graeme M. ; Anthony, Shelagh ; Arrigoni, Francesca I. ; Leiper, James M. ; Vallance, Patrick</creatorcontrib><description>Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor,
S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1
mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(03)01507-9</identifier><identifier>PMID: 12927816</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amidohydrolases - chemistry ; Amidohydrolases - metabolism ; Angiogenesis ; Arginine - analogs & derivatives ; Arginine - biosynthesis ; Arginine - chemistry ; Asymmetric dimethylarginine ; Blotting, Northern ; Cells, Cultured ; Collagen - pharmacology ; Dimethylarginine dimethylaminohydrolase ; Drug Combinations ; Endogenous nitric oxide synthase inhibitors ; Endothelial function ; Endothelial Growth Factors - biosynthesis ; Endothelial Growth Factors - chemistry ; Endothelium, Vascular - cytology ; Gene expression ; Humans ; Immunoblotting ; Intercellular Signaling Peptides and Proteins - biosynthesis ; Intercellular Signaling Peptides and Proteins - chemistry ; Laminin - pharmacology ; Lymphokines - biosynthesis ; Lymphokines - chemistry ; Nitric oxide ; Phenotype ; Plasmids - metabolism ; Proteoglycans - pharmacology ; RNA, Messenger - metabolism ; Space life sciences ; Time Factors ; Transfection ; Tube formation ; Umbilical Veins - cytology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Biochemical and biophysical research communications, 2003-09, Vol.308 (4), p.984-989</ispartof><rights>2003 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-f4ef82613f0a58dfa079ba7190c07f41eb87d32acfb5789179e090d17be0b40a3</citedby><cites>FETCH-LOGICAL-c505t-f4ef82613f0a58dfa079ba7190c07f41eb87d32acfb5789179e090d17be0b40a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X03015079$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12927816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smith, Caroline L.</creatorcontrib><creatorcontrib>Birdsey, Graeme M.</creatorcontrib><creatorcontrib>Anthony, Shelagh</creatorcontrib><creatorcontrib>Arrigoni, Francesca I.</creatorcontrib><creatorcontrib>Leiper, James M.</creatorcontrib><creatorcontrib>Vallance, Patrick</creatorcontrib><title>Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor,
S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1
mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation.</description><subject>Amidohydrolases - chemistry</subject><subject>Amidohydrolases - metabolism</subject><subject>Angiogenesis</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - biosynthesis</subject><subject>Arginine - chemistry</subject><subject>Asymmetric dimethylarginine</subject><subject>Blotting, Northern</subject><subject>Cells, Cultured</subject><subject>Collagen - pharmacology</subject><subject>Dimethylarginine dimethylaminohydrolase</subject><subject>Drug Combinations</subject><subject>Endogenous nitric oxide synthase inhibitors</subject><subject>Endothelial function</subject><subject>Endothelial Growth Factors - biosynthesis</subject><subject>Endothelial Growth Factors - chemistry</subject><subject>Endothelium, Vascular - cytology</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Intercellular Signaling Peptides and Proteins - biosynthesis</subject><subject>Intercellular Signaling Peptides and Proteins - chemistry</subject><subject>Laminin - pharmacology</subject><subject>Lymphokines - biosynthesis</subject><subject>Lymphokines - chemistry</subject><subject>Nitric oxide</subject><subject>Phenotype</subject><subject>Plasmids - metabolism</subject><subject>Proteoglycans - pharmacology</subject><subject>RNA, Messenger - metabolism</subject><subject>Space life sciences</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tube formation</subject><subject>Umbilical Veins - cytology</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVtv1DAQha0K1C6lP6HITwikpszk5vipWvUGUisegKpvlmNPWEMSBzu7Iv-ebHeBxz6NNPrOXM5h7BThHAHLD18AoExSiY_vIHsPWIBI5AFbIEhIUoT8BVv8Q47Yqxh_ACDmpTxkR5jKVFRYLtjPK9fRuJpaHb673vXE7d9G53q_mmzwrY7EtRndxo0T77xdt3qkyJdX90ve0obaeMYfrm9vOP0eAsXofH_GdW-5obblw4p6P04DvWYvG91GOtnXY_bt5vrr5cfk7vPtp8vlXWIKKMakyamp0hKzBnRR2UaDkLUWKMGAaHKkuhI2S7Vp6kJUEoWk-WeLoiaoc9DZMXu7mzsE_2tNcVSdi9tTdE9-HZXISshQpM-CWFUZyLKawWIHmuBjDNSoIbhOh0khqG0c6ikOtfVaQaae4lBy1r3ZL1jXHdn_qr3_M3CxA2YPaeMoqGgc9YasC2RGZb17ZsUfgcSbww</recordid><startdate>20030905</startdate><enddate>20030905</enddate><creator>Smith, Caroline L.</creator><creator>Birdsey, Graeme M.</creator><creator>Anthony, Shelagh</creator><creator>Arrigoni, Francesca I.</creator><creator>Leiper, James M.</creator><creator>Vallance, Patrick</creator><general>Elsevier 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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20030905</creationdate><title>Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype</title><author>Smith, Caroline L. ; Birdsey, Graeme M. ; Anthony, Shelagh ; Arrigoni, Francesca I. ; Leiper, James M. ; Vallance, Patrick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-f4ef82613f0a58dfa079ba7190c07f41eb87d32acfb5789179e090d17be0b40a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amidohydrolases - chemistry</topic><topic>Amidohydrolases - metabolism</topic><topic>Angiogenesis</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - biosynthesis</topic><topic>Arginine - chemistry</topic><topic>Asymmetric dimethylarginine</topic><topic>Blotting, Northern</topic><topic>Cells, Cultured</topic><topic>Collagen - pharmacology</topic><topic>Dimethylarginine dimethylaminohydrolase</topic><topic>Drug Combinations</topic><topic>Endogenous nitric oxide synthase inhibitors</topic><topic>Endothelial function</topic><topic>Endothelial Growth Factors - biosynthesis</topic><topic>Endothelial Growth Factors - chemistry</topic><topic>Endothelium, Vascular - cytology</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Intercellular Signaling Peptides and Proteins - biosynthesis</topic><topic>Intercellular Signaling Peptides and Proteins - chemistry</topic><topic>Laminin - pharmacology</topic><topic>Lymphokines - biosynthesis</topic><topic>Lymphokines - chemistry</topic><topic>Nitric oxide</topic><topic>Phenotype</topic><topic>Plasmids - metabolism</topic><topic>Proteoglycans - pharmacology</topic><topic>RNA, Messenger - metabolism</topic><topic>Space life sciences</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Tube formation</topic><topic>Umbilical Veins - cytology</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Caroline L.</creatorcontrib><creatorcontrib>Birdsey, Graeme M.</creatorcontrib><creatorcontrib>Anthony, Shelagh</creatorcontrib><creatorcontrib>Arrigoni, Francesca I.</creatorcontrib><creatorcontrib>Leiper, James M.</creatorcontrib><creatorcontrib>Vallance, Patrick</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Caroline L.</au><au>Birdsey, Graeme M.</au><au>Anthony, Shelagh</au><au>Arrigoni, Francesca I.</au><au>Leiper, James M.</au><au>Vallance, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2003-09-05</date><risdate>2003</risdate><volume>308</volume><issue>4</issue><spage>984</spage><epage>989</epage><pages>984-989</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor,
S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1
mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12927816</pmid><doi>10.1016/S0006-291X(03)01507-9</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-291X |
| ispartof | Biochemical and biophysical research communications, 2003-09, Vol.308 (4), p.984-989 |
| issn | 0006-291X 1090-2104 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73603172 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amidohydrolases - chemistry Amidohydrolases - metabolism Angiogenesis Arginine - analogs & derivatives Arginine - biosynthesis Arginine - chemistry Asymmetric dimethylarginine Blotting, Northern Cells, Cultured Collagen - pharmacology Dimethylarginine dimethylaminohydrolase Drug Combinations Endogenous nitric oxide synthase inhibitors Endothelial function Endothelial Growth Factors - biosynthesis Endothelial Growth Factors - chemistry Endothelium, Vascular - cytology Gene expression Humans Immunoblotting Intercellular Signaling Peptides and Proteins - biosynthesis Intercellular Signaling Peptides and Proteins - chemistry Laminin - pharmacology Lymphokines - biosynthesis Lymphokines - chemistry Nitric oxide Phenotype Plasmids - metabolism Proteoglycans - pharmacology RNA, Messenger - metabolism Space life sciences Time Factors Transfection Tube formation Umbilical Veins - cytology Vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| title | Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T23%3A36%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dimethylarginine%20dimethylaminohydrolase%20activity%20modulates%20ADMA%20levels,%20VEGF%20expression,%20and%20cell%20phenotype&rft.jtitle=Biochemical%20and%20biophysical%20research%20communications&rft.au=Smith,%20Caroline%20L.&rft.date=2003-09-05&rft.volume=308&rft.issue=4&rft.spage=984&rft.epage=989&rft.pages=984-989&rft.issn=0006-291X&rft.eissn=1090-2104&rft_id=info:doi/10.1016/S0006-291X(03)01507-9&rft_dat=%3Cproquest_cross%3E18830968%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18830968&rft_id=info:pmid/12927816&rft_els_id=S0006291X03015079&rfr_iscdi=true |