Membrane modifications in human erythroleukemia K562 cells during induction of programmed cell death by transforming growth factor β 1 or cisplatin

Abstract

Transforming growth factor beta1 (TGFbeta1) and cisplatin induce apoptosis (programmed cell death, PCD) in human erythroleukemia K562 cells in an additive manner. After PCD was induced in K562 cells, analysis of phospholipid composition, fatty acids and cholesterol content in their membranes showed a decrease in phosphatidylethanolamine and an increase in phosphatidylserine, cardiolipin and phosphatidic acid. Moreover, cisplatin but not TGFbeta1 enhanced sphingomyeline levels in apoptotic cells, whereas TGFbeta1 increased the amount of linoleic acid and, more remarkably, of cholesterol. The combination TGFbeta+ cisplatin produced membrane changes similar to those provoked by each inducer individually. Furthermore, the specific activities of 5-lipoxygenase and cytosolic phospholipase A2, both modulating the physical properties of membranes and membrane-lipid-mediated intracellular signalling, were enhanced by treatment with TGFbeta1 or TGFbeta1 + cisplatin. These findings highlight the profound changes in cell membranes during the biochemical events of the apoptotic pathway.