ヒト臍帯静脈内皮細胞(HUVEC)における Lysophosphatidylcholine(LPC)刺激によるVEGFレセプターのトランスアクチベーション

機関リポジトリ Web Site

書誌事項

タイトル別名
  • ダイ14カイ トクシマ イガクカイ ジュショウ ロンブン ヒト サイタイ ジョウミャク ナイヒ サイボウ HUVEC ニ オケル Lysophosphatidylcholine LPC シゲキ ニ ヨル VEGF レセプター ノ トランスアクチベーション
  • Lysophosphatidylcholine (LPC) transactivates vascular endothelial growth factor (VEGF) receptor via c-Src in HUVEC
  • ヒト サイタイ ジョウミャク ナイヒ サイボウ HUVEC ニオケル Lysophosphatidylcholine LPC シゲキ ニヨル VEGF レセプター ノ トランス アクチベーション

この論文をさがす

抄録

One of the major lipid components of oxidized low density lipoprotein, lysophosphatidylcholine （LPC） is involved in numerous biological processes as a bioactive lipid molecule and has been shown to be involved in the progression of atherosclerosis. As counter-ligands, G２A and GPR４ were identified with high binding affinity for LPC that are belonging to orphan G-protein-coupled receptors （GPCRs） at plasma membranes. Although several GPCR ligands transactivate receptor tyrosine kinases （RTKs）, such as epidermal growth factor receptor, transactivation of RTK by LPC has not yet been reported. Here we observed for the first time that LPC treatment induces tyrosyl phosphorylation of vascular endothelial growth factor （VEGF） receptor２ （fetal liver kinase-１／kinase-insert domain-containing receptor, Flk-１／KDR） in human umbilical vein endothelial cells （HUVEC）. VEGF receptor tyrosine kinase inhibitors, SU１４９８ and VTKi inhibited Flk-１／KDR transactivation by LPC. Furthermore, we examined the effect of the Src family kinases inhibitors, Herbimycin A and PP２ on LPC-induced Flk-１／KDR transactivation. Herbimycin A and PP２ inhibited Flk-１／KDR transactivation in HUVEC, suggesting that c-Src is involved in LPC-induced Flk-１／KDR transactivation. Kinase-inactive （KI） Src transfection also inhibited LPC-induced Flk-１／KDR transactivation. In addition, LPC activated extracellular signal-regulated kinase１／２ and Akt, which are downstream effectors of Flk-１／KDR, and these were inhibited by SU１４９８，VTKi, Herbimycin A, PP２ and KI Src transfection in HUVEC. LPC-mediated HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU１４９８，VTKi, Herbimycin A, PP２and KI Src transfection. It is concluded that c-Src-mediated Flk-１／KDR transactivation by LPC may have important implications for the progression of atherosclerosis.

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ