scholarly journals The effect of various concentrations of nucleobases, nucleosides or glutamine on the incorporation of [3H]thymidine into DNA in rat mesenteric-lymph-node lymphocytes stimulated by phytohaemagglutinin

1990 ◽  
Vol 270 (2) ◽  
pp. 437-440 ◽  
Author(s):  
Z Szondy ◽  
E A Newsholme

1. The rate of [3H]thymidine incorporation into DNA was measured in phytohaemagglutinin-stimulated lymph-node lymphocytes of the rat. 2. Addition of nucleobases or nucleosides to culture medium that already contained 0.2 mM-glutamine had a small stimulatory effect on incorporation. At lower concentrations of glutamine, adenosine (even at 1 microM) caused a marked increase in the rate of incorporation. 3. In the absence of added glutamine, addition of nucleosides or nucleobases markedly increased the rate of incorporation: nucleosides were more effective than nucleobases; and the rate of proliferation in the presence of 10 microM-adenosine plus 10 microM-uridine was similar to that in the presence of optimal concentrations of glutamine. 4. The rate of incorporation was dramatically decreased by an inhibitor of the pathway of pyrimidine nucleotide synthesis de novo. Addition of the pyrimidine nucleosides completely overcame the inhibition; addition of the pyrimidine nucleobases was much less effective. 5. These results indicate that, for proliferation of lymphocytes, glutamine is not essential and can be partially or totally replaced by nucleosides and, to some extent, by nucleobases.

2017 ◽  
Vol 47 (12) ◽  
pp. 2142-2152 ◽  
Author(s):  
Maria Pasztoi ◽  
Joern Pezoldt ◽  
Michael Beckstette ◽  
Christoph Lipps ◽  
Dagmar Wirth ◽  
...  

1991 ◽  
Vol 278 (2) ◽  
pp. 471-474 ◽  
Author(s):  
Z Szondy ◽  
E A Newsholme

1. Addition of concanavalin A to T-cell lymphocytes from rat cervical lymph nodes increases the activity of glutaminase within 1 h and those of carbamoyl-phosphate synthase II and aspartate transcarbamoylase within 3 h. There was a similar time course for the effects of concanavalin A on rates of glutamine utilization, which was increased within 1 h, and on pyrimidine nucleotide synthesis, which was increased by 40% at 2 h and by 100% at 3 h. 2. A delay in the addition of glutamine to the culture medium after addition of concanavalin A caused a decrease in [3H]thymidine incorporation only after 4-6 h. In the absence of glutamine, delay in addition of guanosine or inosine caused a decrease in [3H]thymidine incorporation only after 6-8 h after the addition of concanavalin A. 3. In contrast, a delay in addition of adenosine or uridine to the culture medium had an immediate effect (i.e. within 2 h) on the rate of incorporation of [3H]thymidine. It is suggested that adenosine and uridine have specific effects on proliferation via specific receptors for these nucleosides in the membrane.


1999 ◽  
Author(s):  
D. Damman ◽  
P. B. Bahnson ◽  
R. M. Weigel ◽  
R. E. Isaacson ◽  
H. F. Troutt ◽  
...  

2021 ◽  
Author(s):  
Hans-Georg Sprenger ◽  
Thomas MacVicar ◽  
Amir Bahat ◽  
Kai Uwe Fiedler ◽  
Steffen Hermans ◽  
...  

AbstractCytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–STING–TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33. Deficiency of YME1L causes inflammation in mouse retinas and in cultured cells. It drives the release of mtDNA and a cGAS–STING–TBK1-dependent inflammatory response, which requires SLC25A33 and is suppressed upon replenishment of cellular pyrimidine pools. Overexpression of SLC25A33 is sufficient to induce immune signalling by mtDNA. Similarly, depletion of cytosolic nucleotides upon inhibition of de novo pyrimidine synthesis triggers mtDNA-dependent immune responses in wild-type cells. Our results thus identify mtDNA release and innate immune signalling as a metabolic response to cellular pyrimidine deficiencies.


Author(s):  
Joy Nakawesi ◽  
Konjit Getachew Muleta ◽  
Dragos‐Christian Dasoveanu ◽  
Bengt Johansson‐Lindbom ◽  
Katharina Lahl

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