5-aminoimidazole-4-carboxamide ribonucleoside and AMP-activated protein kinase inhibit signalling through NF-κB.

来自 EBSCO

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作者：

M Katerelos，SJ Mudge，D Stapleton，RB Auwardt，SA Fraser，CG Chen，BE Kemp，DA Power

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摘要：

Activation of nuclear factor-kappa B (NF-B) is one of the most important pro-inflammatory mechanisms in disease. In this study, we show that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an intermediate in nucleoside metabolism, inhibits signalling by NF-B in three cell types, including bovine aortic endothelial cells (BAEC). The block in the NF-B signalling pathway occurred beyond degradation of IB-± and movement of p65 into the nucleus of BAEC. There was, however, reduced binding of NF-B from AICAR-treated cells to a B-consensus oligonucleotide, suggesting that part of the mechanism was a reduction in NF-B DNA-binding activity. Although AICAR is metabolized to ZMP and then adenosine, adenosine had no effect on activation of an NF-B reporter. ZMP, however, activates the metabolic stress-sensing AMP-activated protein kinase (AMPK). Transfection of active AMPK into BAEC reduced NF-B reporter activity compared with a kinase-dead mutant, suggesting that part of the ability of AICAR to inhibit NF-B signalling is due to activation of AMPK. Inhibition of NF-B signalling may be important in the anti-inflammatory action of drugs such as sulfasalazine and methotrexate, which led to the accumulation of AICAR within target cells.

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关键词：

AMP-activated protein kinase AICAR NF-κB BAEC

DOI：

10.1038/icb.2010.44

被引量：

106

年份：

2010