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

Abstract

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-α 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 adenosi..