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.
Current Topics in Medicinal Chemistry
Title:Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation
Volume: 17 Issue: 15
Author(s): Alexandra N. Shin, Chiranjib Dasgupta, Guangyu Zhang, Kala Seal and Lubo Zhang*
Affiliation:
- Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350,United States
Keywords: Cardiomyocyte, Endothelin-1, EED, Fetal, Heart, Proliferation, Proteome.
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.
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Cite this article as:
Shin N. Alexandra, Dasgupta Chiranjib, Zhang Guangyu, Seal Kala and Zhang Lubo*, Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation, Current Topics in Medicinal Chemistry 2017; 17 (15) . https://dx.doi.org/10.2174/1568026617666161116142417
DOI https://dx.doi.org/10.2174/1568026617666161116142417 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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