Induction of metallothionein synthesis by cilostazol in mice and in human cultured neuronal cell lines.
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.
Suzuki
Shinya
S
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan. suzukis@ph.bunri-u.ac.jp
Masui
Yosuke
Y
Ohnuki
Mieko
M
Miyakoda
Goro
G
Mori
Toyoki
T
Nakajima
Katsuyuki
K
Sato
Masao
M
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
D018696:Neuroprotective Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D013777:Tetrazoles; D008668:Metallothionein; D000077407:Cilostazol