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.

Hdl Handle:
http://hdl.handle.net/10147/136809
Title:
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
Affiliation:
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. rmuchekehu@ucsd.edu
Citation:
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. 2008, 44 (3):276-88 Cell Calcium
Journal:
Cell calcium
Issue Date:
Sep-2008
URI:
http://hdl.handle.net/10147/136809
DOI:
10.1016/j.ceca.2007.12.001
PubMed ID:
18215419
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/18215419
Abstract:
We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate (200 microM) and the MEK inhibitor PD98059 (10 microM). We established E2 rapidly activates the novel PKC isoform PKCepsilon, 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 [Ca2+]i. We have demonstrated a novel mechanism by which E2 rapidly modulates [Ca2+]i release from ryanodine-receptor-gated intracellular Ca2+ stores. The signal transduction pathway involves the estrogen receptor coupled to a PKC-PKA-Erk 1/2 signalling pathway.
Item Type:
Article
Language:
en
MeSH:
Calcium; Cell Line; Cyclic AMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Eccrine Glands; Estradiol; Estrogens; Extracellular Signal-Regulated MAP Kinases; Humans; Models, Biological; Protein Kinase C; Ryanodine Receptor Calcium Release Channel; Signal Transduction; Thapsigargin; Time Factors
ISSN:
0143-4160

Full metadata record

DC FieldValue Language
dc.contributor.authorMuchekehu, Ruth Wen
dc.contributor.authorHarvey, Brian Jen
dc.date.accessioned2011-07-25T08:38:44Z-
dc.date.available2011-07-25T08:38:44Z-
dc.date.issued2008-09-
dc.identifier.citation17beta-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. 2008, 44 (3):276-88 Cell Calciumen
dc.identifier.issn0143-4160-
dc.identifier.pmid18215419-
dc.identifier.doi10.1016/j.ceca.2007.12.001-
dc.identifier.urihttp://hdl.handle.net/10147/136809-
dc.description.abstractWe describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate (200 microM) and the MEK inhibitor PD98059 (10 microM). We established E2 rapidly activates the novel PKC isoform PKCepsilon, 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 [Ca2+]i. We have demonstrated a novel mechanism by which E2 rapidly modulates [Ca2+]i release from ryanodine-receptor-gated intracellular Ca2+ stores. The signal transduction pathway involves the estrogen receptor coupled to a PKC-PKA-Erk 1/2 signalling pathway.-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/18215419en
dc.subject.meshCalcium-
dc.subject.meshCell Line-
dc.subject.meshCyclic AMP-Dependent Protein Kinases-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshEccrine Glands-
dc.subject.meshEstradiol-
dc.subject.meshEstrogens-
dc.subject.meshExtracellular Signal-Regulated MAP Kinases-
dc.subject.meshHumans-
dc.subject.meshModels, Biological-
dc.subject.meshProtein Kinase C-
dc.subject.meshRyanodine Receptor Calcium Release Channel-
dc.subject.meshSignal Transduction-
dc.subject.meshThapsigargin-
dc.subject.meshTime Factors-
dc.title17beta-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.en
dc.typeArticleen
dc.contributor.departmentMolecular Medicine Laboratories, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland. rmuchekehu@ucsd.eduen
dc.identifier.journalCell calciumen
dc.description.provinceLeinster-
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