Toxin-Induced Activation of Rat Hepatocyte Prostaglandin Synthesis and Phospholipid Metabolism
Abstract
The effects of microcystin-LR a trichothecene (T-2 toxin) and saxitoxin on membrane lipid mediators of inflammatory processes were evaluated in cultured rat hepatocytes. Microcystin-LR significantly stimulated the release of prostacyclin and thromboxane B(2) in a concentration-dependent manner. The trichothecene toxin, T-2, enhanced the release of prostaglandin F(2)a (PGF(2)a) by 24% (p <0.05) and arachidonic acid by 29% (p <0.05); while saxitoxin failed to cause the release of prostaglandins or arachidonic acid. Incorporation of arachidonic acid into the lipid pool was reduced to 47% (p <0.025) by 1 micromole microcystin-LR. Changes in phospholipid classes indicated that prostaglandin formation induced by microcystin-LR was due to the release of arachidonic acid from the phosphatidylinositol pool. A 10% increase in phosphatidylcholine in hepatocytes treated with microcystin-LR may have resulted from conversion of phosphatidylethanolamine to phosphatidylcholine via the N- methylation pathway. These results indicate that microcystin-LR has important effects on the regulation of inflammatory mediator synthesis in hepatocytes. (AW)
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 22, 1989
- Accession Number
- ADA218039
Entities
People
- Harry B. Hines
- Kulthoum A. Mereish
- Rikki Solow
- Syed M. Naseem
Organizations
- United States Army Medical Research Institute of Infectious Diseases