Choi Bo-Hwa, Lee Da-Hyun, Kim Jin, Kang Ju-Hee, Park Chang-Shin
Department of Pharmacology, Hypoxia-Related Disease Research Center, Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, Korea.
Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea.
Int Neurourol J. 2016 Sep;20(3):182-187. doi: 10.5213/inj.1632718.359. Epub 2016 Sep 23.
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.
一般来说，在用5´-AMP激活蛋白激酶（AMPK）激活剂如5´-氨基咪唑-4-甲酰胺核糖核苷酸（AICAR）或降糖药二甲双胍预处理后，通过对NF-κB磷酸化进行不同的翻译后修饰，脂多糖（LPS）和缺氧诱导的核因子κB（NF-κB）效应均可得到缓解。我们发现，AICAR或二甲双胍通过一种依赖AMPK的机制，作为LPS/NF-κB或缺氧/NF-κB介导的环氧化酶诱导的调节剂，p65-NF-κB的磷酸化和乙酰化之间存在相互作用，包括在人膀胱癌细胞系（T24）中。总之，我们强调了AMPK活性对NF-κB诱导的调节相互作用，特别是在炎症条件或缺氧环境下NF-κB的翻译后磷酸化和乙酰化过程中。
