Poster Presenter

Statins Change Cellular Lipid Metabolism: Yeast As A Model Organism For Investigating The Effects Of Statin Treatment
Agata Leszczynska, Beata Burzynska, Monika Wysocka-Kapcinska, Marek Kiliszek, Danuta Plochocka, Joanna Kaminska, Joanna Rytka and Anna Szkopinska
Poland

Defects in lipid metabolism are associated with a number of severe diseases such as atherosclerosis, obesity and type II diabetes. Hypercholesterolemia is a primary risk factor for coronary artery disease, the major cause of premature death in developed countries. Statins - inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase - are widely used to reduce blood cholesterol levels. Although statin therapy is regarded as well tolerated, serious adverse effects have been reported. Since the yeast Saccharomyces cerevisiae harbors many counterparts of human enzymes involved in lipid synthesizing pathways, conclusions drawn from research with this single cell organism can be useful for studying human metabolic processes. Using our yeast expression system we investigated the effects of statins on the cellular lipid metabolism. We found two significant phenomena. First, cells treated with simvastatin develop an adaptive response compensating for its sterol lowering action. This includes enhanced conversion of sterol precursors into ergosterol, mobilization of steryl esters and increased expression of HMGR gene. Second, statins cause a substantial drop in the level of glycerophospholipids. To conclude, for the first time we showed using yeast expression system that statin treatment introduce changes into cell lipid metabolism.