title: 5-Aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved.
abstract: 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.
authors.affiliation: Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Campus de Bellvitge, E-08907 L'Hospitalet, Spain. jose.lopez@crg.es
authors.forename: José M
authors.initials: JM
authors.lastname: López
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Santidrián
authors.forename: Clara
authors.initials: C
authors.lastname: Campàs
authors.forename: Joan
authors.initials: J
authors.lastname: Gil
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D012263:Ribonucleosides / Q000494:pharmacology*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D000590:Amino Acid Chloromethyl Ketones; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D012263:Ribonucleosides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000620:Aminoimidazole Carboxamide; D013868:Thioinosine; C011651:acadesine; D017868:Cyclic AMP-Dependent Protein Kinases; D020169:Caspases; C001789:4-nitrobenzylthioinosine; D000241:Adenosine