H-1 NMR-visible mobile lipid domains correlate with cytoplasmic lipid bodies in apoptotic T-lymphoblastoid cells

The presence of nuclear magnetic resonance (NMR)-visible mobile lipid (ML d omains in apoptotic lymphoblasts suggests alterations in neutral lipid meta bolism and compartmentation during programmed cell death. The detection of similar ML signals in activated lymphocytes raises questions about common m echanisms of ML formation during apoptosis and upon lymphoblast stimulation . Structure and subcellular localization of ML domains were therefore inves tigated by NMR, fluorescence and electron microscopy in Jurkat T-lymphoblas ts either induced to apoptosis (by anthracyclines or dexamethasone or by se rum deprivation) or activated by phorbol myristate acetate (PMA) plus ionom ycin. ML contents in drug-treated cells correlated linearly with apoptosis, irrespective of the specific inducer and cell cycle arrest phase (r = 0.99 3, P < 0.001). Similar ML levels were measured in drug-induced apoptotic ce lls (A <approximate to> 30-40%) and in non-apoptotic PMA/ionomycin-treated lymphoblasts (72 h), Lower ML contents were instead formed in serum-deprive d apoptotic cells, with respect to controls. Increases in ML signals were a ssociated, in either apoptotic or activated cells, with the accumulation of cytoplasmic, osmophilic lipid bodies (diamcter less than or equal to 1.0 m um), surrounded by own membrane, possessing intramembrane particles. The re sults support the hypothesis that ML are formed in the cytoplasm of drug-in duced apoptotic cells during an early, 'biochemically active' phase of prog rammed cell death. (C) 2001 Elsevier Science B.V. All rights reserved.