Effect of 5-amino-4-imidazolecarboxamide riboside (AICA-riboside) on the purine nucleotide synthesis and growth of rat kidney cells in culture: Study with [15N]aspartate
✍ Scribed by Itzhak Nissim; Marc Yudkoff; Ilana Nissim; Beatrice States
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 572 KB
- Volume
- 138
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Division of Biochemical Development and Molecular Diwaies, The Childrcn'i Hospital of f h r / d d t ~/ p h i a , and Departments of fudiatrics arid Medicine, University of fenn~y/vdnia School of Mcdicine, fhiladelphrd, Pcvmsylvania 7 9 7 04 The present investigation evaluates the effect of AICA-Riboside on the synthesis of purine nucleotides and the growth of normal rat kidney cells in culture. Experiments in the presence and absence of various concentrations of AICA-Ribosidc were conducted with Dulbecco's Modified Eagle's Medium supplemented with either 1 m M ["Nlaspartate or ['4N]aspartate. Addition of 50 pM AICA-Riboside to the incubation medium significantly stimulated intracellular adenine nucleotide concenlrations following incubation for 48 hours. This stimulation was associated with augmented cell growth and DNA concentration.
In contrast, with concentrations above 100 pM of AKA-Kiboside in the incubation medium, there was J remarkable inhibition of cell growth and a significant depletion of intracellular pools of adenine nucleotides a i d DNA. Experiments with ['5N]aspartate showed that the initial rate (0-24 hours) of 16-15NH,ladenine nuclcotide formation from 1 rnM [I5N]aspartate was 38.8 & cI.f.5, 67.9 i 12.5, and 20.1 ? 3.8 p o l h-'/10'' cells in the presence of 0 (control), 50 FM and 500 pM AICA-Riboside, respectively. These observations indicate that the main effect of AICA-Riboside is on the formdtion of AMP from aspartate and IMP via the sequential action of adenylosuccinate synthetase and adenylosuccinate lyase.
The current studies suggest that AICA-Riboside could be used a5 a factor mediating renal cell mitosis in culture. AKA-Riboside has a biphasic effect on the growth of renal epithelial cell5 in culture and on their intracellular purine nucleotides and DNA concenlrdtion.