Membrane modifications in human erythroleukemia K562 cells during induction of programmed cell death by transforming growth factor β1 or cisplatin

Transforming growth factor β1 (TGFβ1) 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 TGFβ1 enhanced sphingomyeline levels in apoptotic cells, whereas TGFβ1 increased the amount of linoleic acid and, more remarkably, of cholesterol. The combination TGFβ1+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 TGFβ1 or TGFβ1+cisplatin. These findings highlight the profound changes in cell membranes during the biochemical events of the apoptotic pathway.