Induction of apoptosis in two mammalian cell lines results in increased levels of fructose‐1,6‐Bisphosphate and CDP‐choline as determined by 31P MRS

Programmed cell death or apoptosis was induced in human promyelocytic leukemia (HL‐60) and Chinese hamster ovary (CHO‐K1) cells using several cytotoxic drugs that have different modes of action, including camptothecin, ceramide, chelerythrine, etoposide, farnesol, geranyl geraniol, and hexadecylphosphocholine. The consequent changes in cellular metabolism were monitored using 31P MRS measurements on intact cells and cell extracts. Cells undergoing programmed cell death exhibited characteristic changes in the levels of glycolytic and phospholipid metabolites. The most significant changes were increases in the concentration of the glycolytic intermediate, fructose‐l,6‐bisphosphate and in the concentration of CDP‐choline, which is an intermediate in phosphatidylcholine biosynthesis. In HL‐60 cells, the increase in fructose‐l,6‐bisphosphate levels could be explained by depletion of cellular NAD(H) levels. All of the agents used to induce apoptosis caused the accumulation of CDP‐choline. Since the resonances of this compound occur in a relatively well resolved region of tissue spectra, it could provide a marker for apoptosis that would allow the noninvasive detection of the process in vivo using 31P MRS measurements.

[1]  K. Brindle,et al.  Mapping of oxygen tension and cell distribution in a hollow-fiber bioreactor using magnetic resonance imaging. , 1997, Biotechnology and bioengineering.

[2]  Jimmy D Bell,et al.  Characterisation of secondary metabolites associated with neutrophil apoptosis , 1996, FEBS letters.

[3]  G. Favre,et al.  Farnesol and geranylgeraniol induce actin cytoskeleton disorganization and apoptosis in A549 lung adenocarcinoma cells. , 1996, Biochemical and biophysical research communications.

[4]  D. Vance,et al.  A Genetic Defect in Phosphatidylcholine Biosynthesis Triggers Apoptosis in Chinese Hamster Ovary Cells* , 1996, The Journal of Biological Chemistry.

[5]  R. Gottlieb,et al.  Mutant cystic fibrosis transmembrane conductance regulator inhibits acidification and apoptosis in C127 cells: possible relevance to cystic fibrosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K. Brindle,et al.  31P NMR measurements of the effects of unsaturated fatty acids on cellular phospholipid metabolism , 1996, Magnetic resonance in medicine.

[7]  L. Zon,et al.  Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis , 1996, Nature.

[8]  R. Gottlieb,et al.  Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Jack Benner,et al.  Activation of Glycosylasparaginase , 1996, The Journal of Biological Chemistry.

[10]  A. Cossarizza,et al.  Control of apoptosis by the cellular ATP level , 1996, FEBS letters.

[11]  S. Orrenius,et al.  Signal transduction pathways in apoptosis. , 1994, Stem cells.

[12]  R. Testi,et al.  Multiple pathways originate at the Fas/APO‐1 (CD95) receptor: sequential involvement of phosphatidylcholine‐specific phospholipase C and acidic sphingomyelinase in the propagation of the apoptotic signal. , 1995, The EMBO journal.

[13]  P. Voziyan,et al.  Mechanism of farnesol cytotoxicity: further evidence for the role of PKC-dependent signal transduction in farnesol-induced apoptotic cell death. , 1995, Biochemical and biophysical research communications.

[14]  G. Navon,et al.  Mechanism of action of the antineoplastic drug lonidamine: 31P and 13C nuclear magnetic resonance studies. , 1995, Cancer research.

[15]  A. Columbano.  Cell death: Current difficulties in discriminating apoptosis from necrosis in the context of pathological processes in vivo , 1995, Journal of cellular biochemistry.

[16]  L. Milas,et al.  Apoptosis in murine tumors treated with chemotherapy agents. , 1995, Anti-cancer drugs.

[17]  T. Merchant,et al.  Comparison of relative changes in phosphatic metabolites and phospholipids after irradiation. , 1995, Radiation research.

[18]  T G Cotter,et al.  Cell death (apoptosis) in cell culture systems. , 1995, Trends in biotechnology.

[19]  F. Mollinedo,et al.  Intracellular Alkalinization Suppresses Lovastatin-induced Apoptosis in HL-60 Cells through the Inactivation of a pH-dependent Endonuclease (*) , 1995, The Journal of Biological Chemistry.

[20]  R. Gillies,et al.  Increase of GPC Levels in Cultured Mammalian Cells during Acidosis. A 31P MR Spectroscopy Study Using a Continuous Bioreactor System , 1995, Magnetic resonance in medicine.

[21]  A. Eastman,et al.  Apoptosis in an Interleukin-2-dependent Cytotoxic T Lymphocyte Cell Line Is Associated with Intracellular Acidification , 1995, The Journal of Biological Chemistry.

[22]  Y. Hannun,et al.  Ceramide: an intracellular signal for apoptosis. , 1995, Trends in biochemical sciences.

[23]  Y. Hirabayashi,et al.  Induction of apoptotic DNA fragmentation and cell death by natural ceramide , 1995, FEBS letters.

[24]  J. Kerr,et al.  Anatomical methods in cell death. , 1995, Methods in cell biology.

[25]  Y. Masuda,et al.  Geranylgeraniol is a potent inducer of apoptosis in tumor cells. , 1995, Journal of biochemistry.

[26]  L. Smets,et al.  BCL-2 expression and mitochondrial activity in leukemic cells with different sensitivity to glucocorticoid-induced apoptosis. , 1994, Blood.

[27]  C. Winterford,et al.  Apoptosis. Its significance in cancer and cancer Therapy , 1994, Cancer.

[28]  S. Grant,et al.  Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C. , 1994, Cancer research.

[29]  C. J. Walkey,et al.  Overexpression of rat liver CTP:phosphocholine cytidylyltransferase accelerates phosphatidylcholine synthesis and degradation. , 1994, The Journal of biological chemistry.

[30]  D. Green,et al.  Dicing with death: dissecting the components of the apoptosis machinery. , 1994, Trends in biochemical sciences.

[31]  P. Voziyan,et al.  Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity. , 1993, The Biochemical journal.

[32]  Z. Darżynkiewicz,et al.  Different patterns of apoptosis of HL‐60 cells induced by cycloheximide and camptothecin , 1993, Journal of cellular physiology.

[33]  A. Yoshida,et al.  Role of calcium ion in induction of apoptosis by etoposide in human leukemia HL-60 cells. , 1993, Biochemical and biophysical research communications.

[34]  M. Collins,et al.  The control of apoptosis in mammalian cells. , 1993, Trends in biochemical sciences.

[35]  C. Tepper,et al.  Resistance of mitochondrial DNA to degradation characterizes the apoptotic but not the necrotic mode of human leukemia cell death , 1993, Journal of cellular biochemistry.

[36]  Z. Darżynkiewicz,et al.  The cell cycle related differences in susceptibility of HL-60 cells to apoptosis induced by various antitumor agents. , 1993, Cancer research.

[37]  A. Eastman,et al.  Etoposide-induced apoptosis in human HL-60 cells is associated with intracellular acidification. , 1993, Cancer research.

[38]  F. Mollinedo,et al.  Early and selective induction of apoptosis in human leukemic cells by the alkyl-lysophospholipid ET-18-OCH3. , 1993, Biochemical and biophysical research communications.

[39]  C. Dive,et al.  Non-genotoxic hepatocarcinogenesis in vitro: the FaO hepatoma line responds to peroxisome proliferators and retains the ability to undergo apoptosis. , 1993, Journal of cell science.

[40]  K. Ang,et al.  Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies. , 1993, International journal of radiation biology.

[41]  H. Steller,et al.  Programmed cell death during Drosophila embryogenesis. , 1993, Development.

[42]  J. Ruíz-Cabello,et al.  Phospholipid metabolites as indicators of cancer cell function , 1992, NMR in biomedicine.

[43]  J. Griffiths,et al.  The contribution made by cell death and oxygenation to 31P MRS observations of tumour energy metabolism , 1992, NMR in biomedicine.

[44]  W. Negendank,et al.  Studies of human tumors by MRS: A review , 1992, NMR in biomedicine.

[45]  W. Reutter,et al.  Hexadecylphosphocholine inhibits translocation of CTP:choline-phosphate cytidylyltransferase in Madin-Darby canine kidney cells. , 1992, The Journal of biological chemistry.

[46]  S. Clarke,et al.  Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. , 1992, Annual review of biochemistry.

[47]  R. Gillies,et al.  Iteration of hybridoma growth and productivity in hollow fiber bioreactors using 31P NMR , 1991, Magnetic resonance in medicine.

[48]  H. Thielmann,et al.  31P NMR studies of cultured human tumor cells. Influence of ph on phospholipid metabolite levels and the detection of cytidine 5′‐diphosphate choline , 1990, NMR in biomedicine.

[49]  K. Brindle,et al.  31P-NMR studies of glucose and glutamine metabolism in cultured mammalian cells. , 1990, Biochimica et biophysica acta.

[50]  M. Walport,et al.  Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. , 1989, The Journal of clinical investigation.

[51]  J. Cohen,et al.  Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications: a review. , 1989, Cancer research.

[52]  A. Tolkovsky,et al.  Na+/H+ exchange is the major mechanism of pH regulation in cultured sympathetic neurons: Measurements in single cell bodies and neurites using a fluorescent pH indicator , 1987, Neuroscience.

[53]  C. K. Pearson,et al.  Cellular euthanasia mediated by a nuclear enzyme: a central role for nuclear ADP-ribosylation in cellular metabolism , 1987 .

[54]  M. Fujiwara,et al.  Effects of Ca2+ on ethanolaminephosphotransferase and cholinephosphotransferase in rabbit platelets. , 1986, Journal of biochemistry.

[55]  P. Matthews,et al.  Energetics of human muscle: Exercise‐induced ATP depletion , 1986, Magnetic resonance in medicine.

[56]  S. J. Berger,et al.  Metabolic consequences of DNA damage: DNA damage induces alterations in glucose metabolism by activation of poly (ADP-ribose) polymerase. , 1986, Biochemical and biophysical research communications.

[57]  D. Vance,et al.  Regulation of phosphatidylcholine biosynthesis. , 1984, Biochimica et biophysica acta.

[58]  S. J. Berger,et al.  Poly(ADP-ribose) Polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis. , 1983, Biochemistry.

[59]  E. McConkey.  Molecular evolution, intracellular organization, and the quinary structure of proteins. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. B. Moon,et al.  Determination of intracellular pH by 31P magnetic resonance. , 1973, The Journal of biological chemistry.