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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Multiple signaling is involved in endostatin-mediated apoptosis in ECV 304 endothelial cells
Bin Ren1, Yuan Wang, Kenneth Ndebele
1School of Life Science, University of Science and Technology of China, Hefei 230027, China. bin_ren@hms.harvard.edu <bin_ren@hms.harvard.edu>
Abstract:
Apoptosis of vascular endothelial cells is associated with the regression of angiogenesis. Endostatin is a potential anti-angiogenic drug, but the effects of endostatin on apoptotic machinery in endothelial cells largely remain unclear. In the present study, human endostatin was expressed in E. Coli to induce apoptosis in endothelial cells. It was found that the expressed human endostatin specifically affected the viability of the ECV 304 in a dose-dependent manner. Endostatin induced apoptosis in these cells in a caspase-dependent manner, and endostatin-mediated apoptosis is associated with several apoptotic signaling pathways including overloading of intracellular magnesium and calcium, as well as regulation of p53 and Bcl 2 expression.
Insights
Endostatin induces programmed cell death (apoptosis) in endothelial cells via a caspase-dependent pathway. This anti-angiogenic mechanism involves key signaling molecules like p53 and Bcl-2.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Apoptosis of vascular endothelial cells is crucial for regulating angiogenesis.
- Endostatin is a promising anti-angiogenic therapeutic, but its precise effects on endothelial cell apoptosis pathways are not fully understood.
Purpose of the Study:
- To investigate the effects of human endostatin on endothelial cell apoptosis.
- To elucidate the specific molecular mechanisms and signaling pathways involved in endostatin-induced apoptosis.
Main Methods:
- Expression of human endostatin in E. coli.
- Treatment of ECV 304 endothelial cells with expressed endostatin.
- Assessment of cell viability, apoptosis, and key signaling molecules (caspases, p53, Bcl-2, intracellular ions).
Main Results:
- Expressed human endostatin reduced ECV 304 cell viability in a dose-dependent manner.
- Endostatin triggered apoptosis through a caspase-dependent mechanism.
- Apoptosis was linked to intracellular magnesium and calcium overload and altered p53 and Bcl-2 expression.
Conclusions:
- Human endostatin effectively induces apoptosis in endothelial cells.
- The process is mediated by caspases and involves significant alterations in apoptotic signaling pathways.
- Findings provide insight into endostatin's anti-angiogenic potential at the cellular level.
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