title: Plasminogen N-terminal activation peptide modulates the activity of angiostatin-related peptides on endothelial cell proliferation and migration.
abstract: Angiostatin, a potent inhibitor of angiogenesis, is derived from the fibrinolytic proenzyme, plasminogen, by enzymatic processing. Plasminogen N-terminal activation peptide (PAP) is one of the products concomitantly released aside from angiostatin (kringles 1-4) and mini-plasminogen (kringle 5 plus the catalytic domain) when plasminogen is processed. To determine whether PAP alone or together with the angiostatin-related peptides derived from the processing of plasminogen modulate the proliferation and motility of endothelial cells, we have generated a recombinant PAP and used it to study its effects on endothelial cells in the presence and absence of the angiostatin-related peptides. Our results showed that PAP alone slightly increased the migration but not the proliferation of endothelial cells. However, in the presence of the angiostatin-related peptides, PAP attenuated the inhibitory activity of the angiostatin-related peptides on the proliferation and migration of endothelial cells. The inhibitory effect of PAP on the angiostatin-related peptides could be due to its binding to the kringle domains of the latter peptides.
authors.affiliation: Department of Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
authors.forename: Moyuru
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tamura
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimonaka
mesh_terms: D043165:Angiostatic Proteins / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018082:Kringles / Q000502:physiology; D010958:Plasminogen / Q000008:administration & dosage*
chemical_list: D043165:Angiostatic Proteins; D010958:Plasminogen