Anti-angiogenic effect of tetraacetyl-phytosphingosine

:  In a search for the wound healing accelerators, we found that tetraacetyl‐phytosphingosine (TAPS), a sphingolipid metabolite produced by phytosphingosine acetylation, has significant inhibitory potential on healing of rabbit ear wound. As angiogenesis is fundamental to proper wound healing, we ex...

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Veröffentlicht in:Experimental dermatology 2007-04, Vol.16 (4), p.311-317
Hauptverfasser: Kwon, Yoo Bin, Kim, Chang Deok, Kim, Bo Joong, Kim, Min-Young, Park, Chang Seo, Yoon, Tae-Jin, Seo, Young-Joon, Suhr, Ki-Beom, Park, Jang-Kyu, Lee, Jeung-Hoon
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container_end_page 317
container_issue 4
container_start_page 311
container_title Experimental dermatology
container_volume 16
creator Kwon, Yoo Bin
Kim, Chang Deok
Kim, Bo Joong
Kim, Min-Young
Park, Chang Seo
Yoon, Tae-Jin
Seo, Young-Joon
Suhr, Ki-Beom
Park, Jang-Kyu
Lee, Jeung-Hoon
description :  In a search for the wound healing accelerators, we found that tetraacetyl‐phytosphingosine (TAPS), a sphingolipid metabolite produced by phytosphingosine acetylation, has significant inhibitory potential on healing of rabbit ear wound. As angiogenesis is fundamental to proper wound healing, we examined the effect of TAPS on angiogenesis using human umbilical vein endothelial cells cultured in vitro. TAPS markedly decreased vascular endothelial growth factor (VEGF)‐induced chemotactic migration and capillary‐like tube formation. Recognizing its inhibitory potential on angiogenesis, we further investigated the action mechanism of TAPS. TAPS significantly inhibited VEGF‐induced proteolytic enzyme production, including matrix metalloproteinase‐2, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1. TAPS also suppressed VEGF‐induced phosphorylation of p42/44 extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase. In addition, TAPS abolished VEGF‐induced intracellular calcium increase, measured using laser scanning confocal microscopy. Together, these results suggest that TAPS exerts its inhibitory action on angiogenesis through the inhibition of mitogen‐activated protein kinase activation and intracellular calcium increase, thereby affecting the process of wound healing negatively.
doi_str_mv 10.1111/j.1600-0625.2006.00530.x
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As angiogenesis is fundamental to proper wound healing, we examined the effect of TAPS on angiogenesis using human umbilical vein endothelial cells cultured in vitro. TAPS markedly decreased vascular endothelial growth factor (VEGF)‐induced chemotactic migration and capillary‐like tube formation. Recognizing its inhibitory potential on angiogenesis, we further investigated the action mechanism of TAPS. TAPS significantly inhibited VEGF‐induced proteolytic enzyme production, including matrix metalloproteinase‐2, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1. TAPS also suppressed VEGF‐induced phosphorylation of p42/44 extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase. In addition, TAPS abolished VEGF‐induced intracellular calcium increase, measured using laser scanning confocal microscopy. 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As angiogenesis is fundamental to proper wound healing, we examined the effect of TAPS on angiogenesis using human umbilical vein endothelial cells cultured in vitro. TAPS markedly decreased vascular endothelial growth factor (VEGF)‐induced chemotactic migration and capillary‐like tube formation. Recognizing its inhibitory potential on angiogenesis, we further investigated the action mechanism of TAPS. TAPS significantly inhibited VEGF‐induced proteolytic enzyme production, including matrix metalloproteinase‐2, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1. TAPS also suppressed VEGF‐induced phosphorylation of p42/44 extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase. In addition, TAPS abolished VEGF‐induced intracellular calcium increase, measured using laser scanning confocal microscopy. 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derivatives</subject><subject>Sphingosine - chemistry</subject><subject>Sphingosine - pharmacology</subject><subject>tetraacetyl-phytosphingosine</subject><subject>Umbilical Veins - cytology</subject><subject>Urokinase-Type Plasminogen Activator - metabolism</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><subject>Wound Healing - drug effects</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkclOwzAURS0EgjL8AuoGdgkvcTxEYsPUMlSwARWxsRznpbikSYhT0f49CalgizfXks_1s44JGQbgB-06m_sBB_CAh8wPAbgPwCj4qy0y-D3YJgOIgXtcANsj-87NAQJBBdsle22ymFIxIPyiaKyni5ktZ1hYM8QsQ9MMy2zYYFNrbbBZ5171vm5KV73bYlY6W-Ah2cl07vBokwfkZXTzfHXrTZ7Gd1cXE89ENAIPQymSGBnjnBrOEpFi2gZLUBojdcaFQCPDLNYSIxHKNIm0kZxHAU-ZjiN6QE77e6u6_Fyia9TCOoN5rgssl04JCHnMgLag7EFTl87VmKmqtgtdr1UAqnOm5qpTozo1qnOmfpypVVs93sxYJgtM_4obSS1wsgG0MzrPal0Y6_44yWTMw44777kvm-P63w9QN6_X7aate33dugZXv3Vdfyje_ZuaPo7V6IFOg7f7SxXTb9OEliM</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Kwon, Yoo Bin</creator><creator>Kim, Chang Deok</creator><creator>Kim, Bo Joong</creator><creator>Kim, Min-Young</creator><creator>Park, Chang Seo</creator><creator>Yoon, Tae-Jin</creator><creator>Seo, Young-Joon</creator><creator>Suhr, Ki-Beom</creator><creator>Park, Jang-Kyu</creator><creator>Lee, Jeung-Hoon</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</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><scope>7X8</scope></search><sort><creationdate>200704</creationdate><title>Anti-angiogenic effect of tetraacetyl-phytosphingosine</title><author>Kwon, Yoo Bin ; Kim, Chang Deok ; Kim, Bo Joong ; Kim, Min-Young ; Park, Chang Seo ; Yoon, Tae-Jin ; Seo, Young-Joon ; Suhr, Ki-Beom ; Park, Jang-Kyu ; Lee, Jeung-Hoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4340-e287b9e55663c65b7ded65b5be8cc8af677ec82f9a8e4728db4ac866416d5a943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acetylation</topic><topic>angiogenesis</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>Calcium - metabolism</topic><topic>Cell Movement</topic><topic>Cells, Cultured</topic><topic>Dermatology</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - enzymology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Humans</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Medical sciences</topic><topic>mitogen-activated protein kinase</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Phosphorylation - drug effects</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>proteolytic enzyme</topic><topic>Rabbits</topic><topic>Signal Transduction - drug effects</topic><topic>Sphingosine - analogs &amp; 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As angiogenesis is fundamental to proper wound healing, we examined the effect of TAPS on angiogenesis using human umbilical vein endothelial cells cultured in vitro. TAPS markedly decreased vascular endothelial growth factor (VEGF)‐induced chemotactic migration and capillary‐like tube formation. Recognizing its inhibitory potential on angiogenesis, we further investigated the action mechanism of TAPS. TAPS significantly inhibited VEGF‐induced proteolytic enzyme production, including matrix metalloproteinase‐2, urokinase‐type plasminogen activator and plasminogen activator inhibitor‐1. TAPS also suppressed VEGF‐induced phosphorylation of p42/44 extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase. In addition, TAPS abolished VEGF‐induced intracellular calcium increase, measured using laser scanning confocal microscopy. Together, these results suggest that TAPS exerts its inhibitory action on angiogenesis through the inhibition of mitogen‐activated protein kinase activation and intracellular calcium increase, thereby affecting the process of wound healing negatively.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17359337</pmid><doi>10.1111/j.1600-0625.2006.00530.x</doi><tpages>7</tpages></addata></record>
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subjects Acetylation
angiogenesis
Animals
Biological and medical sciences
calcium
Calcium - metabolism
Cell Movement
Cells, Cultured
Dermatology
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelial Cells - enzymology
Extracellular Signal-Regulated MAP Kinases - metabolism
Humans
JNK Mitogen-Activated Protein Kinases - metabolism
Matrix Metalloproteinase 2 - metabolism
Medical sciences
mitogen-activated protein kinase
Neovascularization, Physiologic - drug effects
Phosphorylation - drug effects
Plasminogen Activator Inhibitor 1 - metabolism
proteolytic enzyme
Rabbits
Signal Transduction - drug effects
Sphingosine - analogs & derivatives
Sphingosine - chemistry
Sphingosine - pharmacology
tetraacetyl-phytosphingosine
Umbilical Veins - cytology
Urokinase-Type Plasminogen Activator - metabolism
Vascular Endothelial Growth Factor A - pharmacology
Wound Healing - drug effects
title Anti-angiogenic effect of tetraacetyl-phytosphingosine
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