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Melatonin sensitizes human myometrial cells to oxytocin in a protein kinase C alpha/extracellular-signal regulated kinase-dependent manner.

Title: Melatonin sensitizes human myometrial cells to oxytocin in a protein kinase C alpha/extracellular-signal regulated kinase-dependent manner.
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Name(s): Sharkey, James T, author
Cable, Casey, author
Olcese, James, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2010-06-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified the human myometrium as a target for melatonin (MEL), the neuroendocrine output signal coding for circadian night. The purpose of this study was to determine the signaling pathway underlying the effects of MEL on contractility and the contractile machinery in immortalized human myometrial cells. To ascertain the signaling pathway of MEL leading to its effects on myometrial contractility in vitro, we performed gel retraction assays with cells exposed to iodo-MEL (I-MEL) with or without oxytocin and the Rho kinase inhibitor Y27632. I-MEL effects on inositol trisphosphate (IP(3))/diacylglycerol (DAG)/protein kinase C (PKC) signaling were also investigated. Additionally, we assayed for caldesmon phosphorylation and ERK1/2 activation. I-MEL was found to activate PKC alpha via the phospholipase C/IP(3)/DAG signaling pathway, which was confirmed by PKC enzyme assay. I-MEL did not affect myosin light chain phosphatase activity, and its effects on contractility were insensitive to Rho kinase inhibition. I-MEL did increase phosphorylation of ERK1/2 and caldesmon, which was inhibited by the MAPK kinase inhibitor PD98059 or the PKC inhibitor C1. MEL sensitizes myometrial cells to subsequent procontractile signals in vitro through activation of the phospholipase C/IP(3)/DAG signaling pathway, resulting in specific activation of PKC alpha and ERK1/2, thereby phosphorylating caldesmon, which increases actin availability for myosin binding and cross-bridging. In vivo, this sensitization would provide a mechanism for the increased nocturnal uterine contractility and labor that has been observed in late-term human pregnancy.
Identifier: FSU_pmch_20382690 (IID), 10.1210/jc.2009-2137 (DOI), PMC2902072 (PMCID), 20382690 (RID), 20382690 (EID), jc.2009-2137 (PII)
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902072.
Subject(s): Blotting, Western
Calmodulin-Binding Proteins/metabolism
Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases/physiology
Female
Humans
Immunoprecipitation
Inosine Triphosphate/metabolism
Melatonin/pharmacology
Muscle Contraction/physiology
Myocytes, Smooth Muscle/drug effects
Myocytes, Smooth Muscle/enzymology
Myocytes, Smooth Muscle/metabolism
Myometrium/cytology
Myometrium/drug effects
Myosin Light Chains/metabolism
Myosin-Light-Chain Kinase/metabolism
Myosins/metabolism
Oxytocin/pharmacology
Phosphorylation
Protein Kinase C-alpha/antagonists & inhibitors
Protein Kinase C-alpha/physiology
Signal Transduction/drug effects
rho-Associated Kinases/antagonists & inhibitors
rho-Associated Kinases/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_20382690
Owner Institution: FSU
Is Part Of: The Journal of clinical endocrinology and metabolism.
1945-7197
Issue: iss. 6, vol. 95

Choose the citation style.
Sharkey, J. T., Cable, C., & Olcese, J. (2010). Melatonin sensitizes human myometrial cells to oxytocin in a protein kinase C alpha/extracellular-signal regulated kinase-dependent manner. The Journal Of Clinical Endocrinology And Metabolism. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_20382690