Details

Autor(en) / Beteiligte

• Kim, Byoung Ywong
• Cho, Chi-Heum
• Song, Dae-Kyu
• Mun, Kyo-Cheol
• Suh, Seong-Il
• Kim, Sang-Pyo
• Shin, Dong-Hoon
• Jang, Byeong-Churl
• Kwon, Taeg Kyu
• Cha, Soon-Do
• Bae, Insoo
• Bae, Jae Hoon

Titel

Ciglitizone inhibits cell proliferation in human uterine leiomyoma via activation of store-operated Ca super(2+) channels

Ist Teil von

• American Journal of Physiology: Cell Physiology, 2005-02, Vol.288 (2), p.C389-C395

Erscheinungsjahr

2005

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• This study investigated the acute effects of a peroxisome proliferator- activated receptor (PPAR)- gamma ligand, ciglitizone, on cell proliferation and intracellular Ca super(2+) signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca super(2+) concentration ([Ca super(2+)] sub(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 mu M) induced greater inhibition of cell proliferation in uterine leiomyoma than in myometrium. Ciglitizone also dose- dependently increased [Ca super(2+)] sub(i) in both myometrium and uterine leiomyoma; these [Ca super(2+)] sub(i) increases were inhibited by PPAR- gamma antagonists and raloxifene. Ciglitizone-induced [Ca super(2+)] sub(i) increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca super(2+)] sub(i) increase as well. The initial [Ca super(2+)] sub(i) increase in both myometrium and uterine leiomyoma resulted from the release of Ca super(2+) by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca super(2+)] sub(i) increase was observed only in uterine leiomyoma because of a Ca super(2+) influx via an activation of store-operated Ca super(2+) channels (SOCCs). Cell proliferation was inhibited and secondary [Ca super(2+)] sub(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 [Ca super(2+)] sub(i) through the activation of SOCCs, especially in human uterine leiomyoma.