Consequences of adenosine deaminase deficiency on thymocyte metabolism

European Journal of Immunology
L ThuillierP H Cartier

Abstract

Using 2'-deoxycoformycin inhibition of adenosine deaminase as a model of adenosine deaminase deficiency, the effects of 10 microM 2'-deoxyadenosine (dAdo) on the metabolism of concanavalin A (Con A)-stimulated rat thymocytes were studied. When dAdo and Con A were added simultaneously, a strong inhibition of the incorporation of [3H]thymidine (84%); [3H]uridine (98%) and L-[3H] leucine (46%) in the acid-insoluble fraction, and of [14C]formate (78%) and H14CO-3 (43%) uptake is observed after 48 h of incubation. When dAdo is added after 12 h of Con A stimulation, no such inhibition is observed, but when added after 24 h of stimulation, there is an enhancement of blastogenesis as measured by nucleic acid, protein, and purine and pyrimidine base synthesis. More detailed studies of thymocytes stimulated by Con A for 0-72 h, followed by short-term incubation periods with dAdo (1-5 h), revealed that thymocyte metabolism becomes progressively less sensitive to dAdo-mediated inhibition during the course of blastogenesis. These results suggest that (a) the inhibition of ribonucleotide reductase is not the only mechanism involved in the inhibition of blastogenesis by dAdo and that (b) such inhibition of thymocyte metabolism is essentially ...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·D A CarsonJ E Seegmiller
Jan 1, 1978·Annual Review of Biochemistry·I H Fox, W N Kelley
May 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·R L WortmannI H Fox
Jan 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·A CohenD W Martin
Oct 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·B S MitchellW N Kelley
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Dec 15, 1977·Biochemical Pharmacology·J F Smyth, K R Harrap
Sep 20, 1976·Clinica Chimica Acta; International Journal of Clinical Chemistry·P Cartier, M Hamet

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Citations

Feb 1, 1983·Clinical Biochemistry·R W Watts
Jul 1, 1988·Scandinavian Journal of Immunology·J G ScharenbergB J Zegers

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