17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3 |
| |
Authors: | Muchekehu Ruth W Harvey Brian J |
| |
Institution: | Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland. |
| |
Abstract: | We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca(2+) (Ca(2+)](i)) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal Ca(2+)](i), however exposure of cells to E2 in the presence of the microsomal Ca(2+) ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in Ca(2+)](i) compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in Ca(2+)](i). The E2-induced increase in Ca(2+)](i) was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100muM). The estrogen receptor antagonist ICI 182,780 (1muM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of Ca(2+)](i) from ryanodine-receptor-gated stores. The E2-induced effect on Ca(2+)](i) could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10muM), the protein kinase A (PKA) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate (200muM) and the MEK inhibitor PD98059 (10muM). We established E2 rapidly activates the novel PKC isoform PKCvarepsilon, PKA and Erk 1/2 MAPK in a PKCdelta and estrogen-receptor-dependent manner. The E2-induced effect was specific to 17beta-estradiol, as other steroids had no effect on Ca(2+)](i). We have demonstrated a novel mechanism by which E2 rapidly modulates Ca(2+)](i) release from ryanodine-receptor-gated intracellular Ca(2+) stores. The signal transduction pathway involves the estrogen receptor coupled to a PKC-PKA-Erk 1/2 signalling pathway. |
| |
Keywords: | 17β -Estradiol Ryanodine receptors PKC PKA Erk 1/2 Calcium Rapid non-genomic NCL-SG3 Sweat gland |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|