López José M, Santidrián Antonio F, Campàs Clara, Gil Joan
Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Universitat de Barcelona, Campus de Bellvitge, E-08907 L'Hospitalet, Spain.
Biochem J. 2003 Mar 15;370(Pt 3):1027-32. doi: 10.1042/BJ20021053.
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-氨基咪唑-4-甲酰胺（AICA）核苷是嘌呤核苷酸生物合成的前体，可诱导Jurkat细胞凋亡。AICA核苷进入细胞对于这种效应是必需的，因为加入核苷转运抑制剂硝基苄硫肌苷可完全保护Jurkat细胞免于凋亡。腺苷而非其他核苷也可保护Jurkat细胞免于AICA核苷诱导的凋亡。凋亡效应是半胱天冬酶依赖性的，因为半胱天冬酶9和3被激活，且半胱天冬酶抑制剂苄氧羰基-Val-Ala-Asp-氟甲基酮（Z-VAD.fmk）可阻断凋亡。此外，AICA核苷可诱导线粒体细胞色素c释放。AICA核苷磷酸化成为AICA核苷酸（ZMP）后，在某些细胞类型中是AMP活化蛋白激酶（AMPK）的特异性激活剂。然而，AICA核苷在Jurkat细胞中并不激活AMPK。此外，AICA核苷磷酸化抑制剂5-碘杀结核菌素并不抑制Jurkat细胞的凋亡。这些结果表明，AICA核苷在Jurkat细胞中诱导凋亡独立于ZMP合成和AMPK激活。
