Quantitative profiling of the rat heart myoblast secretome reveals differential responses to hypoxia and re-oxygenation stress
Author
Li, Xin
Ren, Yan
Sorokin, Vitaly
Poh, Kian Keong
Ho, Hee Hwa
Lee, Chuen Neng
de Kleijn, Dominique
Lim, Sai Kiang
Tam, James P.
Sze, Siu Kwan
Date of Issue
2014School
School of Biological Sciences
Version
Accepted version
Abstract
Secretion of bioactive mediators regulates cell interactions with the microenvironment in tissue homeostasis and wound healing processes. We assessed the cardiomyocyte secretory response to hypoxia with the aim of identifying key mediators of tissue pathology and repair after ischemic heart attack. We profiled the secretome of rat H9C2 cardiomyoblast cells subjected to 16h hypoxia followed by 24h re-oxygenation using iTRAQ and label-free quantitative proteomics. A total of 860 and 2007 proteins were identified in the iTRAQ and label-free experiments respectively. Among these proteins, 1363 were identified as being secreted proteins, including mediators of critical cellular functions that were modulated by hypoxia/re-oxygenation stress (SerpinH1, Ppia, Attractin, EMC1, Postn, Thbs1, Timp1, Stip1, Robo2, Fat1). Further analysis indicated that hypoxia is associated with angiogenesis, inflammation, and remodeling of the extracellular matrix (ECM), whereas subsequent re-oxygenation was instead associated with modified secretion of proteins involved in suppression of inflammation, ECM modification, and decreased output of anti-apoptosis proteins. These data indicate that hypoxia and subsequent re-oxygenation modify the cardiomyocyte secretome in order to mitigate cellular injury and promote healing. The identified changes in cardiomyocyte secretome advance our current understanding of cardiac biology in ischemia/reperfusion injury and may lead to the identification of novel prognostic biomarker.
Subject
DRNTU::Science::Biological sciences::Cytology
Type
Journal Article
Series/Journal Title
Journal of proteomics
Rights
© 2014 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Proteomics, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.jprot.2013.12.025].
Collections
http://dx.doi.org/10.1016/j.jprot.2013.12.025
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