31P NMR characterization of cellular metabolism during dexamethasone induced apoptosis in human leukemic cell lines.
31P NMR has been used to study the effects of dexamethasone on phosphorus metabolism in one dexamethasone (dex)-sensitive (CEM-C7) and three different dex-resistant (CEM-C1, CEM-4R4, and CEM-ICR27) human leukemic cell lines. The use of these cell lines, containing widely varying amounts of glucocorticoid receptors, made it possible to evaluate the receptor-mediated contributions to the modes of action of dexamethasone in these cells. To evaluate the effects of dexamethasone without any significant contribution from experimental conditions, all the experiments were done with parallel controls. Results obtained showed: 1) significantly different levels of phosphorylethanolamine (PE) and phosphorylcholine (PC) among cell lines, suggesting significant differences in phospholipid metabolism; 2) the dexamethasone induced reduction of phosphomonoester (PE+PC), ATP, and metabolic rates probably through glucocorticoid receptor mediated mechanisms; 3) the dexamethasone induced stimulation of cellular metabolism in a process which seems to be independent of glucocorticoid receptors; and 4) the dexamethasone induced alkaline shift of intracellular pH in all the cell lines except ICR27. The reduction in PME levels seems to be an earlier step in dexamethasone-induced apoptosis than the reduction in ATP. The degree of alkaline shift was found to correlate with the number of glucocorticoid receptors present. The possible involvement of phospholipid metabolites as second messengers in dexamethasone-induced apoptosis is discussed.
Adebodun
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Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0653.
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JF
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D003907:Dexamethasone / Q000494:pharmacology*; D004983:Ethanolamines / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D010758:Phosphorus / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004983:Ethanolamines; D010767:Phosphorylcholine; D010758:Phosphorus; C005448:phosphorylethanolamine; D003907:Dexamethasone; D000255:Adenosine Triphosphate