{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nakamura T"],"funding":["Japan Society for the Promotion of Science"],"pagination":["42327-42337"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9057965"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(69)"],"pubmed_abstract":["Vascular endothelial cells cover the luminal surface of blood vessels in a monolayer. Proliferation of these cells is crucial for the repair of damaged endothelial monolayers. In the present study, we identified a zinc complex, Zn(ii)2,9-dimethyl-1,10-phenanthroline (Zn-12), that stimulates the proliferation of bovine aortic endothelial cells in a culture system. No such stimulatory activity was observed for the ligand alone or in combination with other metals; however, the ligand combined with iron weakly stimulated the proliferation, as evidenced by the [<sup>3</sup>H]thymidine incorporation assay. Inorganic zinc weakly but significantly stimulated proliferation, and intracellular accumulation of zinc was similar between inorganic zinc and Zn-12 treatment, suggesting that the mechanisms by which Zn-12 stimulates vascular endothelial cell proliferation contain processes that differ from those by which inorganic zinc stimulates proliferation. Although expression of endogenous fibroblast growth factor-2 (FGF-2) and its receptor FGFR-1 was unchanged by Zn-12, both siRNA-mediated knockdown of FGF-2 and FGFR inhibition partly but significantly suppressed the stimulation of vascular endothelial cell proliferation by Zn-12, indicating that the zinc complex activates the FGF-2 pathway to stimulate proliferation. Phosphorylation of ERK1/2 and MAPKs was induced by Zn-12, and PD98059, a MEK1 inhibitor, significantly suppressed the stimulatory effect of Zn-12 on vascular endothelial cell proliferation. Therefore, it is suggested that Zn-12 activates the FGF-2 pathway <i>via</i> activation of ERK1/2 signaling to stimulate vascular endothelial cell proliferation, although FGF-2-independent mechanisms are also involved in the stimulation. Zn-12 and related compounds may be promising molecular probes to analyze biological systems of vascular endothelial cells."],"journal":["RSC advances"],"pubmed_title":["Zn(ii)2,9-dimethyl-1,10-phenanthroline stimulates cultured bovine aortic endothelial cell proliferation."],"pmcid":["PMC9057965"],"funding_grant_id":["JP 19K16361","JP 19K07089","JP 15K14992","JP 18K06638"],"pubmed_authors":["Ogata F","Fujiwara Y","Hara T","Yoshida E","Fujie T","Yamamoto C","Takita R","Nakamura T","Kawasaki N","Kaji T","Uchiyama M"],"additional_accession":[]},"is_claimable":false,"name":"Zn(ii)2,9-dimethyl-1,10-phenanthroline stimulates cultured bovine aortic endothelial cell proliferation.","description":"Vascular endothelial cells cover the luminal surface of blood vessels in a monolayer. Proliferation of these cells is crucial for the repair of damaged endothelial monolayers. In the present study, we identified a zinc complex, Zn(ii)2,9-dimethyl-1,10-phenanthroline (Zn-12), that stimulates the proliferation of bovine aortic endothelial cells in a culture system. No such stimulatory activity was observed for the ligand alone or in combination with other metals; however, the ligand combined with iron weakly stimulated the proliferation, as evidenced by the [<sup>3</sup>H]thymidine incorporation assay. Inorganic zinc weakly but significantly stimulated proliferation, and intracellular accumulation of zinc was similar between inorganic zinc and Zn-12 treatment, suggesting that the mechanisms by which Zn-12 stimulates vascular endothelial cell proliferation contain processes that differ from those by which inorganic zinc stimulates proliferation. Although expression of endogenous fibroblast growth factor-2 (FGF-2) and its receptor FGFR-1 was unchanged by Zn-12, both siRNA-mediated knockdown of FGF-2 and FGFR inhibition partly but significantly suppressed the stimulation of vascular endothelial cell proliferation by Zn-12, indicating that the zinc complex activates the FGF-2 pathway to stimulate proliferation. Phosphorylation of ERK1/2 and MAPKs was induced by Zn-12, and PD98059, a MEK1 inhibitor, significantly suppressed the stimulatory effect of Zn-12 on vascular endothelial cell proliferation. Therefore, it is suggested that Zn-12 activates the FGF-2 pathway <i>via</i> activation of ERK1/2 signaling to stimulate vascular endothelial cell proliferation, although FGF-2-independent mechanisms are also involved in the stimulation. Zn-12 and related compounds may be promising molecular probes to analyze biological systems of vascular endothelial cells.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2025-04-05T13:23:38.609Z","creation":"2025-04-05T13:23:38.609Z"},"accession":"S-EPMC9057965","cross_references":{"pubmed":["35516781"],"doi":["10.1039/d0ra06731h"]}}