Inhibition of type I and type II phospholipase A2 by phosphatidyl-ethanolamine linked to polymeric carriers

Biochemistry
Phyllis DanS Yedgar

Abstract

We have previously shown that cell surface proteoglycans protect the cell membrane from the action of extracellular phospholipase A2 (PLA2) enzymes [Dan, P., Nitzan, D. W., Dagan, A., Ginsburg, I., and Yedgar, S. (1996) FEBS Lett. 383, 75-78]. Cell-impermeable PLA2 inhibitors (ExPLIs) were prepared by linking phosphatidylethanolamine (PE) to polymeric carriers, specifically, carboxymethylcellulose, heparin, or hyaluronic acid. The structure of these inhibitors enables the incorporation of their PE moiety into the membrane while the polymer remains at the membrane surface. In the present study, we show that the ExPLIs are effective inhibitors of the hydrolysis of different phospholipids in biological (Escherichia coli) and model (phospholipid vesicle) membranes, by diverse types of PLA2 enzymes, specifically human recombinant synovial fluid and C. atrox (type II), as well as Naja mocambique and porcine pancreatic (type I) PLA2. It is proposed that the external polymers of the ExPLIs, which are anchored to the membrane by the PE, mimic the naturally occurring cell surface proteoglycans and similarly protect membranes from the action of exogenous PLA2.

Citations

May 29, 2002·Thrombosis Research·Rado Nosál, Viera Jancinová
May 14, 2003·Cellular Signalling·Sajal Chakraborti
Nov 18, 2000·Biochimica Et Biophysica Acta·S YedgarE Schnitzer
Sep 19, 2006·Biochimica Et Biophysica Acta·Saul YedgarDavid Shoseyov
Jul 9, 2003·Critical Care Medicine·Grietje Ch BeckSaul Yedgar
Nov 24, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sarit OfferDavid Shoseyov
May 2, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·M KrimskyM Ligumsky

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