Ciglitizone inhibits cell proliferation in human uterine leiomyoma via activation of store-operated Ca2+ channels

Authors
Byoung Ywong KimChi-Heum ChoDae-Kyu SongKyo-Cheol MunSeong-Il SuhSang-Pyo KimDong-Hoon ShinByeong-Churl JangTaeg Kyu KwonSoon-Do ChaInsoo BaeJae Hoon Bae
Department
Dept. of Physiology (생리학); Dept. of Obstetrics & Gynecology (산부인과학); Dept. of Biochemistry (생화학); Dept. of Microbiology (미생물학); Dept. of Pathology (병리학); Dept. of Molecular Medicine (분자의학); Dept. of Preventive Medicine (예방의학); Dept. of Immunology (면역학)
Issue Date
2005
Citation
American Journal of Physiology : Cell Physiology, Vol.288(2) : 389-395, 2005
ISSN
0363-6143
Abstract
This study investigated the acute effects of a peroxisome proliferator-activated receptor (PPAR)-γ ligand, ciglitizone, on cell proliferation and intracellular Ca2+ signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured with fura-2 AM, and cellular viabilities were determined by viable cell count and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay. Ciglitizone (100 μM) induced greater inhibition of cell proliferation in uterine leiomyoma than in myometrium. Ciglitizone also dose-dependently increased [Ca2+]i in both myometrium and uterine leiomyoma; these [Ca2+]i increases were inhibited by PPAR-γ antagonists and raloxifene. Ciglitizone-induced [Ca2+]i increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca2+]i increase as well. The initial [Ca2+]i increase in both myometrium and uterine leiomyoma resulted from the release of Ca2+ by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca2+]i increase was observed only in uterine leiomyoma because of a Ca2+ influx via an activation of store-operated Ca2+ channels (SOCCs). Cell proliferation was inhibited and secondary [Ca2+]i increase in uterine leiomyoma was attenuated by cotreatment of ciglitizone with a SOCC blocker, lanthanum. The results suggest that ciglitizone inhibits cell proliferation and increases [Ca2+]i through the activation of SOCCs, especially in human uterine leiomyoma.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34910
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
Keimyung Author(s)
송대규; 배재훈; 조치흠; 차순도; 문교철; 서성일; 김상표; 장병철; 신동훈; 권택규
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