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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiopoietin-Like Protein 1
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Angiopoietin-like Proteins
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Angiopoietins / genetics
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Angiopoietins / metabolism*
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Blood Vessels / cytology
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Blood Vessels / embryology*
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Endothelial Cells / cytology
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Endothelial Cells / metabolism*
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Gene Silencing
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Intercellular Signaling Peptides and Proteins / metabolism*
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Oligodeoxyribonucleotides, Antisense / administration & dosage
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Oligodeoxyribonucleotides, Antisense / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Zebrafish / embryology*
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Zebrafish / genetics
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Angiopoietin-Like Protein 1
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Angiopoietin-like Proteins
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Angiopoietins
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Angptl1 protein, zebrafish
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Intercellular Signaling Peptides and Proteins
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Oligodeoxyribonucleotides, Antisense
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Proto-Oncogene Proteins
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Zebrafish Proteins
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angptl2b protein, zebrafish
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt