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The proteasome is involved in angiogenesis
T Oikawa1, T Sasaki, M Nakamura
1Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Rinshoken, Japan. oikawa@rinshoken.or.jp
Biochemical and Biophysical Research Communications
|May 26, 1998
Summary
The proteasome, a cellular protease, is crucial for angiogenesis, the formation of new blood vessels. Inhibiting the proteasome with lactacystin effectively blocks this process in both in vivo and in vitro models.
Area of Science:
- Molecular Biology
- Cell Biology
- Physiology
Background:
- The proteasome is an intracellular protease complex with a threonine active site.
- It plays vital roles in cell cycle, antigen presentation, and apoptosis.
- Its function in multicellular organisms remains largely unexplored due to limited experimental models.
Purpose of the Study:
- To investigate the proteasome's role in angiogenesis.
- To utilize lactacystin, a specific proteasome inhibitor, for experimental validation.
Main Methods:
- In vivo neovascularization assay using chick embryo chorioallantoic membrane.
- In vitro angiogenesis model using endothelial cell tube formation on Matrigel.
- Measurement of plasminogen activator production by endothelial cells.
- Assessment of intracellular proteasome activity.
Main Results:
- Lactacystin treatment almost completely prevented in vivo neovascularization.
- In vitro vascular endothelial tube formation was inhibited by lactacystin in a dose-dependent manner.
- Endothelial cell production of plasminogen activator, crucial for angiogenesis, was suppressed by lactacystin.
- Inhibition of proteasome activity correlated with suppressed angiogenesis.
Conclusions:
- The proteasome is actively involved in the process of angiogenesis.
- Targeting the proteasome may offer therapeutic strategies for conditions involving angiogenesis.
- This study provides evidence for the proteasome's significance in physiological and pathological angiogenesis.