5-Aminoimidazole-4-carboxamide (AICA) riboside, a precursor of purine nucleotide biosynthesis, induces apoptosis in Jurkat cells. Incorporation of AICAriboside into the cells is necessary for this effect since addition of nitrobenzylthioinosine, a nucleoside-transport inhibitor, completely protects Jurkat cells from apoptosis. Adenosine, but not other nucleosides, also protects Jurkat cells from AICAriboside-induced apoptosis. The apoptotic effect is caspase-dependent since caspases 9 and 3 are activated and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) blocks apoptosis. Furthermore, AICAriboside induces mitochondrial cytochrome c release. AICAriboside, when phosphorylated to AICAribotide (ZMP), is a specific activator of the AMP-activated protein kinase (AMPK) in certain cell types. However, AICAriboside does not activate AMPK in Jurkat cells. Moreover, 5-iodotubercidin, an inhibitor of AICAriboside phosphorylation, does not inhibit apoptosis in Jurkat cells. These results indicate that AICAriboside induces apoptosis independently of ZMP synthesis and AMPK activation in Jurkat cells.
- 5-aminoimidazole-4-carboxamide (AICA) riboside
Abbreviations used: ACC, acetyl-CoA carboxylase; AICAriboside, 5-aminoimidazole-4-carboxamide riboside; AMPK, AMP-activated protein kinase; MAP kinase, mitogen-activated protein kinase; MTT, 3,(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide; NBTI, nitrobenzylthioinosine; PARP, poly(ADP-ribose) polymerase; PI, propidium iodide; ZMP, AICAribotide; Z-VAD.fmk, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone.
- The Biochemical Society, London ©2003