期刊
LIFE SCIENCES
卷 99, 期 1-2, 页码 18-23出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2013.07.013
关键词
Pigment epithelium-derived factor; Cardiomyocyte; Apoptosis; Phospholipase A(2); Fas
资金
- Natural Science Foundation of China [81200150, 81200151, 30971060, 81270402, 81070183]
Aims: Cardiovascular diseases cause significant morbidity and mortality worldwide. Recently, our research team demonstrated that a multifunctional cytokine, pigment epithelium-derived factor (PEDF), plays a critical role in regulating myocardial infarction. However, few researchers have studied the molecular mechanisms by which PEDF and its receptors influence the pathophysiology of cardiovascular disease. We tested the hypothesis that PEDF affects cardiomyocyte apoptosis under hypoxic conditions and determined the role that its receptors phospholipase A(2) (PLA(2)) and laminin receptor play in this process. Main methods: Cardiomyocytes were isolated from neonatal mice and treated with PEDF under normoxic and hypoxic conditions; then, apoptosis was assessed using Annexin V/PI staining and flow cytometry. Western blotting and immunofluorescence staining were used to detect PEDF receptor expression, and siRNA knockdown of PEDF receptors was performed to determine which receptor was involved in mediating cardiomyocyte apoptosis. Key findings: Our results demonstrated that PEDF increased cardiomyocyte apoptosis during hypoxia via Fas and that PEDF receptors were expressed on cardiomyocyte cell membranes. Furthermore, siRNA experiments indicated that the PEDF receptor PLA(2) was responsible for inducing cardiomyocyte apoptosis via the Fas pathway. Significance: PEDF promoted Fas-induced cardiomyocyte apoptosis via its receptor PLA(2). (C) 2013 Published by Elsevier Inc.
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