title: Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation.
abstract: Hypoxia is a fetal stressor that leads to the production of endothelin-1 (ET-1). Previous work has shown that ET-1 treatment leads to the premature terminal differentiation of fetal cardiomyocytes. However, the precise mechanism is unknown. We tested the hypothesis that the fetal cardiomyocyte proteome will be greatly altered due to ET-1-treatment, which reveals a potential molecular mechanism of ET-1-induced terminal differentiation. Over a thousand proteins were detected in the fetal cardiomyocytes and among them 75 proteins were significantly altered due to ET-1 treatment. Using IPA pathway analysis, the merged network depicted several key proteins that appeared to be involved in regulating proliferation, including: EED, UBC, ERK1/2, MAPK, Akt, and EGFR. EED protein, which is associated with regulating proliferation via epigenetic mechanisms, is of particular interest. Herein we propose a model of the molecular mechanism by which ET-1 induced cardiomyocyte terminal differentiation occurs.
authors.affiliation: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States.
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Shin
authors.affiliation: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States.
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Dasgupta
authors.affiliation: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Loyola Marymount University, Los Angeles, California, United States.
authors.forename: Kala
authors.initials: K
authors.lastname: Seal
authors.affiliation: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, United States.
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019332:Endothelin-1
keywords: Cardiomyocyte; EED; Endothelin-1; Fetal; Heart; Proliferation; Proteome