Controls of nuclear factor-kappa B signaling activity by 5'-AMP-activated protein kinase activation with examples in human bladder cancer cells

Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor kappa B (NF-κB) effects are alleviated through differential posttranslational modification of NF-κB phosphorylation after pretreatment with 5'-AMP-activated protein kinase (AMPK) activators such as 5'-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found that AICAR or metformin acts as a regulator of LPS/NF-κB-or hypoxia/NF-κB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-κB phosphorylation and acetylation, including in a human bladder cancer cell line (T24). In summary, we highlighted the regulatory interactions of AMPK activity on NF-κB induction, particularly in posttranslational phosphorylation and acetylation of NF-κB under inflammatory conditions or hypoxia environment.