Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 158, Issue 1, Pages 46-53Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2010.12.106
Keywords
Endothelial progenitor cell; Estrogen; Estrogen receptor; Caveolae; Caveolin-1
Categories
Funding
- Natural Science Foundation of Guangdong [05300602]
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Background: The mechanism that estrogen (E-2) increases the number of endothelial progenitor cells (EPC) is largely unknown. Here we used E-2-conjugated bovine serum albumin (E-2-BSA, membrane impermeable) to investigate whether the membrane estrogen receptor (mER) and its related protein caveolin-1 (CAV-1) are involved in these processes. Methods and results: E-2-BSA promoted [H-3]-thymidine incorporation of EPC through increasing CAV-1 expression via mER (ER alpha, but not ER beta or GPR30). Both cholesterol depletion and CAV-1 knockdown with use of CAV-1 siRNA significantly attenuated E-2-BSA-induced [H-3]-thymidine incorporation. Western blot showed that E-2-BSA increased membrane CAV-1 protein expression 12 h after treatment, whereas mRNA levels of CAV-1 were augmented until 24 h after E-2-BSA treatment. Furthermore, pre-incubated EPC with ICI 182780 (a specific ER antagonist), LY 294002 (a selective PI3K inhibitor) or PD 98059 (a specific ERK1/2 inhibitor) before E-2-BSA inhibited the late-stage effect of E-2-BSA (>= 24 h) on up-regulation of CAV-1 mRNA and protein expression. Pulse chase results demonstrated that E-2-BSA inhibited lysosome-mediated degradation of CAV-1 protein at the early stage (<= 12 h), and then resulted in the increased CAV-1 protein. Conclusion: In the present work we demonstrated that E-2-BSA promotes EPC proliferation through mER ERa in CAV-1-dependent manner: prolonging the stability of CAV-1 protein through quick inhibition of the lysosomal degradation pathway at the early stage (<= 12 h) and up-regulating CAV-1 at transcription levels through PI3K/ERK1/2 signaling pathway at the late stage (>= 24 h). These data indicated that a there is a novel mechanism of E-2-BSA in the regulation of EPC proliferation through CAV-1. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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