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Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation

[ Vol. 17 , Issue. 15 ]

Author(s):

Alexandra N. Shin, Chiranjib Dasgupta, Guangyu Zhang, Kala Seal and Lubo Zhang*   Pages 1788 - 1802 ( 15 )

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.

Keywords:

Cardiomyocyte, Endothelin-1, EED, Fetal, Heart, Proliferation, Proteome.

Affiliation:

Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, Loyola Marymount University, Los Angeles, California, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350

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