E2–BSA activates caveolin-1 via PI3K/ERK1/2 and lysosomal degradation pathway and contributes to EPC proliferation
| Autor: | Yu Li, Qiuling Xiang, Zhi Tan, Guiping Lin, Li-Jun Zhou, Yu-Hong Cui, Ting-Huai Wang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Membrane estrogen receptor
biology medicine.diagnostic_test business.industry Serum albumin Endothelial progenitor cell Molecular biology Western blot Caveolin 1 Immunology cardiovascular system biology.protein Medicine Signal transduction Bovine serum albumin Cardiology and Cardiovascular Medicine business PI3K/AKT/mTOR pathway |
| Zdroj: | International Journal of Cardiology. 158:46-53 |
| ISSN: | 0167-5273 |
| Popis: | 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 [ 3 H]-thymidine incorporation of EPC through increasing CAV-1 expression via mER (ERα, but not ERβ or GPR30). Both cholesterol depletion and CAV-1 knockdown with use of CAV-1 siRNA significantly attenuated E 2 -BSA-induced [ 3 H]-thymidine incorporation. Western blot showed that E 2 -BSA increased membrane CAV-1 protein expression 12h after treatment, whereas mRNA levels of CAV-1 were augmented until 24h after E 2 -BSA treatment. Furthermore, pre-incubated EPC with ICI 182780 (a specific ER antagonist), LY 294002 (a selective PI 3 K inhibitor) or PD 98059 (a specific ERK1/2 inhibitor) before E 2 -BSA inhibited the late-stage effect of E 2 -BSA (≥24h) 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 (≤12h), 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（ERα）in CAV-1-dependent manner: prolonging the stability of CAV-1 protein through quick inhibition of the lysosomal degradation pathway at the early stage (≤12h) and up-regulating CAV-1 at transcription levels through PI 3 K/ERK1/2 signaling pathway at the late stage (≥24h). These data indicated that a there is a novel mechanism of E 2 -BSA in the regulation of EPC proliferation through CAV-1. |
| Databáze: | OpenAIRE |
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