31P and 13C NMR studies of isolated perfused hematopoietic cells from leukemic mice.
The myeloproliferative leukemic virus (MPLV) induces within 2-3 weeks a massive infiltration of the adult mouse liver by hematopoietic leukemic cells. Since the metabolism of the infiltrated organ might be correlated with an interaction of two cell populations, it was decided to study the isolated hematopoietic cells separately. The metabolism of these cells embedded in an agarose gel and perfused with labeled substrates was investigated using 31P and 13C NMR. Using [1-13C]glucose as precursor, sequential 13C NMR spectra showed that the hematopoietic cells were able to store glucose as [1-13C]glycogen and to metabolize it through the glycolytic pathway to give [3-13C]lactate as sole end-product. The liver neoglucogenic substrates: [2-13C]pyruvate and [3-13C]alanine are not metabolized by these cells. This suggests that the tricarboxylic acid cycle was not efficient. To investigate further the glycolytic properties of the cells, 10 mM sodium azide was added to the medium containing [1-13C]glucose. When compared to the aerobic conditions, a 40% decrease of nucleotides (0.10 vs 0.17 mumole NTP/10(9) cells), a degradation of [1-13C]glycogen and an increase of ca 35% of the glycolytic rate were observed. The analysis of 13C NMR spectra of the perfusates at the end of the perfusion indicates a total conversion of [1-13C]glucose into [3-13C]lactate and [3-13C]pyruvate under anaerobic conditions. These results permit a better understanding of the metabolism of the perfused leukemic livers which are extensively infiltrated by these hematopoietic cells.
Mégnin
F
F
Institut Curie, Biologie, (INSERM U.219), Centre Universitaire, Orsay, France.
Nedelec
J F
JF
Dimicoli
J L
JL
Lhoste
J M
JM
D000818:Animals; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice