title: Induction of Syndecan-4 by Organic-Inorganic Hybrid Molecules with a 1,10-Phenanthroline Structure in Cultured Vascular Endothelial Cells.
abstract: Organic-inorganic hybrid molecules constitute analytical tools used in biological systems. Vascular endothelial cells synthesize and secrete proteoglycans, which are macromolecules consisting of a core protein and glycosaminoglycan side chains. Although the expression of endothelial proteoglycans is regulated by several cytokines/growth factors, there may be alternative pathways for proteoglycan synthesis aside from downstream pathways activated by these cytokines/growth factors. Here, we investigated organic-inorganic hybrid molecules to determine a variant capable of analyzing the expression of syndecan-4, a transmembrane heparan-sulfate proteoglycan, and identified 1,10-phenanthroline (o-Phen) with or without zinc (Zn-Phen) or rhodium (Rh-Phen). Bovine aortic endothelial cells in culture were treated with these compounds, and the expression ofsyndecan-4mRNA and core proteins was determined by real-time reverse transcription polymerase chain reaction and Western blot analysis, respectively. Our findings indicated thato-Phen and Zn-Phen specifically and strongly induced syndecan-4 expression in cultured vascular endothelial cells through activation of the hypoxia-inducible factor-1α/β pathway via inhibition of prolyl hydroxylase-domain-containing protein 2. These results demonstrated an alternative pathway involved in mediating induction of endothelial syndecan-4 expression and revealed organic-inorganic hybrid molecules as effective tools for analyzing biological systems.
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. 3b13669@ed.tus.ac.jp.
authors.forename: Takato
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. 3b14641@ed.tus.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. 3b11082@ed.tus.ac.jp.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. 3a15702@ed.tus.ac.jp.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. eyoshida@rs.tus.ac.jp.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.affiliation: Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan. yasuyuki@toyaku.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, Japan. yamamoto@phar.toho-u.ac.jp.
authors.forename: Chika
authors.initials: C
authors.lastname: Yamamoto
authors.affiliation: Department of Chemistry, Faculty of Science, Tokyo University of Science, Shinjuku 162-8601, Japan. ssaito@rs.kagu.tus.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan. t-kaji@rs.tus.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaji
mesh_terms: D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D053671:Syndecan-4 / Q000096:biosynthesis*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010618:Phenanthrolines; D011509:Proteoglycans; D053671:Syndecan-4; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; C025205:1,10-phenanthroline
keywords: 1,10-phenanthroline; bioorganometallics; endothelial cells; proteoglycan; syndecan-4