5-aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved
5-aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved
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DOI：
10.1042/bj20021053
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发表时间：
2003-03-15
影响因子：
4.1
通讯作者：
Gil, J
中科院分区：
文献类型：
--
作者：
López, JM;Santidrián, AF;Gil, J
5-氨基咪唑-4-甲酰胺（AICA）核苷，嘌呤核苷酸生物合成的前体，诱导Jurkat细胞凋亡。将AICA核苷掺入细胞中对于这种效果是必要的，因为添加核苷转运抑制剂硝基苄基硫代肌苷完全保护Jurkat细胞免于凋亡。腺苷，而不是其他核苷，也保护Jurkat细胞从AICA核苷诱导的凋亡。细胞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，并且半胱天冬酶抑制剂苄氧基羰基-Val-Ala-Asp-氟甲基酮（Z-VAD. fetamine）阻断细胞凋亡。此外，AICA核糖苷诱导线粒体细胞色素c释放。AICA核苷，当磷酸化为AICA核苷酸（ZMP）时，是某些细胞类型中AMP活化蛋白激酶（AMPK）的特异性激活剂。然而，AICA核苷不激活Jurkat细胞中的AMPK。此外，5-iodotubercidin，AICA核苷磷酸化的抑制剂，不抑制Jurkat细胞的凋亡。这些结果表明，AICA核苷在Jurkat细胞中不依赖于ZMP合成和AMPK活化而诱导细胞凋亡。
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.