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c-Jun triggers apoptosis in human vascular endothelial cells
1Division of Biomedical Sciences, University of California, Riverside 92521, USA. nanping.wang@ucr.edu
Circulation Research
|September 4, 1999
Summary
Overexpressing the transcription factor c-Jun in endothelial cells (ECs) triggers apoptosis. Inhibiting c-Jun with TAM67 reduces EC death, suggesting c-Jun is a key regulator of programmed cell death in vascular endothelium.
Area of Science:
- Molecular Biology
- Cell Biology
- Endothelial Cell Function
Background:
- Transcription factor c-Jun is induced by stimuli that affect endothelial cell (EC) function.
- Understanding c-Jun's role in EC physiology is crucial for vascular health.
Purpose of the Study:
- To investigate the role of c-Jun in endothelial cell apoptosis.
- To determine if c-Jun overexpression is sufficient to induce EC death.
Main Methods:
- Utilized a tetracycline-regulated adenoviral system for c-Jun overexpression in human umbilical vein ECs.
- Assessed apoptosis using ELISA for DNA fragmentation, DNA laddering, and TUNEL assays.
- Employed TAM67, a dominant-negative c-Jun mutant, to abrogate endogenous c-Jun/activator protein-1 activation.
Main Results:
- Specific c-Jun expression triggered EC apoptosis, confirmed by multiple assays.
- Tetracycline effectively suppressed c-Jun overexpression and prevented apoptosis.
- Caspase-associated mechanisms were implicated, as cysteine protease inhibitors blocked apoptosis.
- Overexpression of TAM67 attenuated H2O2-induced EC apoptosis, indicating c-Jun's role in mediating cell death.
Conclusions:
- c-Jun acts as a proapoptotic molecule in endothelial cells.
- c-Jun plays a significant role in regulating the programmed cell death pathway in vascular endothelium.