title: Cooperative interaction of Angiopoietin-like proteins 1 and 2 in zebrafish vascular development.
abstract: Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase/Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in endothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Niikura
authors.forename: Tohru
authors.initials: T
authors.lastname: Morisada
authors.forename: Masaki
authors.initials: M
authors.lastname: Akao
authors.forename: Takashi
authors.initials: T
authors.lastname: Urano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D036341:Intercellular Signaling Peptides and Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D029961:Zebrafish Proteins; C504920:Angptl1 protein, zebrafish; C504921:angptl2b protein, zebrafish