Membrane modifications in human erythroleukemia K562 cells during induction of programmed cell death by transforming growth factor beta 1 or cisplatin.
Transforming growth factor beta 1 (TGF beta 1) 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 TGF beta 1 enhanced sphingomyeline levels in apoptotic cells, whereas TGF beta 1 increased the amount of linoleic acid and, more remarkably, of cholesterol. The combination TGF beta 1 + 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 TGF beta 1 or TGF beta 1 + cisplatin. These findings highlight the profound changes in cell membranes during the biochemical events of the apoptotic pathway.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
M
M
Maccarrone
W E
WE
Nieuwenhuizen
H F
HF
Dullens
M V
MV
Catani
G
G
Melino
G A
GA
Veldink
J F
JF
Vliegenthart
A
A
Finazzo Agrò
D017209:Apoptosis / Q000187:drug effects*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D002945:Cisplatin / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D008563:Membrane Lipids; D010743:Phospholipids; D016212:Transforming Growth Factor beta; D002784:Cholesterol; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D002945:Cisplatin