In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 288, No. 2 ( 2005-02), p. C389-C395
Abstract:
This study investigated the acute effects of a peroxisome proliferator-activated receptor (PPAR)-γ ligand, ciglitizone, on cell proliferation and intracellular Ca 2+ signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca 2+ concentration ([Ca 2+ ] 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 [Ca 2+ ] i in both myometrium and uterine leiomyoma; these [Ca 2+ ] i increases were inhibited by PPAR-γ antagonists and raloxifene. Ciglitizone-induced [Ca 2+ ] i increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca 2+ ] i increase as well. The initial [Ca 2+ ] i increase in both myometrium and uterine leiomyoma resulted from the release of Ca 2+ by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca 2+ ] i increase was observed only in uterine leiomyoma because of a Ca 2+ influx via an activation of store-operated Ca 2+ channels (SOCCs). Cell proliferation was inhibited and secondary [Ca 2+ ] 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 2+ ] i through the activation of SOCCs, especially in human uterine leiomyoma.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00154.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477334-X
SSG:
12
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