title: Induction of metallothionein synthesis by cilostazol in mice and in human cultured neuronal cell lines.
abstract: In this study, we examined the effect of Cilostazol to induce metallothionein (MT) in vivo and in vitro. Intraperitoneal injection of Cilostazol increased the expression of both MT-1 and MT-2 mRNA and total MT protein in the mouse liver. Cilostazol also augmented MT-1 mRNA levels in the murine brain. In vitro exposure to Cilostazol significantly augmented intracellular MT protein levels in cultured human brain microvascular endothelial cells (HBMEC) and in the neuroblastoma cell line IMR32. Taken together, these findings suggest that Cilostazol is an inducer of MT in the murine liver and brain, and that it has the potential to directly induce MT in cells. The contribution of the anti-oxidative effect of MT to the anti-stroke effect of Cilostazol was discussed.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan. suzukis@ph.bunri-u.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Masui
authors.forename: Mieko
authors.initials: M
authors.lastname: Ohnuki
authors.forename: Goro
authors.initials: G
authors.lastname: Miyakoda
authors.forename: Toyoki
authors.initials: T
authors.lastname: Mori
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakajima
authors.forename: Masao
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D045744:Cell Line, Tumor; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D013777:Tetrazoles; D008668:Metallothionein; D000077407:Cilostazol