Related Experiment Videos
Induction of endothelial monolayer permeability by phosphatidate
1Experimental Cell Research Laboratory, The Methodist Research Institute, Indianapolis, Indiana 46202, USA.dkenglish@msn.com
Journal of Cellular Biochemistry
|August 27, 1999
Summary
Phosphatidate increases endothelial cell permeability by activating a tyrosine kinase pathway and calcium signaling. This lipid may physiologically regulate endothelial barrier function, particularly when presented on neutrophil membranes.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Phosphatidate and related lipids can activate endothelial cells.
- The impact of phosphatidate on endothelial monolayer barrier integrity was previously unreported.
Purpose of the Study:
- To investigate the effect of phosphatidate on endothelial monolayer permeability.
- To elucidate the mechanisms underlying phosphatidate-induced changes in endothelial barrier function.
Main Methods:
- Assessed endothelial monolayer permeability using in vitro assays.
- Utilized various phosphatidate chain lengths, including dioctanoyl (di-C8) phosphatidate.
- Employed inhibitors of phosphatidate phosphohydrolase (PAP), tyrosine kinases, and tyrosine phosphatases.
- Measured intracellular calcium (Ca2+) levels and receptor binding.
- Examined the effects of phosphatidate-enriched neutrophil plasma membranes.
Main Results:
- Phosphatidate significantly increased endothelial monolayer permeability.
- This effect was potentiated by inhibiting PAP and involved tyrosine kinase activation and intracellular Ca2+ mobilization.
- Phosphatidate acted via a specific receptor, not through non-specific detergent effects or as a metabolite.
Conclusions:
- Phosphatidate is a physiological modulator of endothelial monolayer permeability.
- It exerts its effects through a receptor-linked, tyrosine kinase-dependent pathway.
- This process leads to Ca2+ mobilization and subsequent endothelial cell activation.