AMPK alpha 2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

作者：Gongol Brendan; Marin Traci; Peng I Chen; Woo Brian; Martin Marcy; King Stephanie; Sun Wei; Johnson David A; Chien Shu^*; Shyy John Y J

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(8): 3161-3166.

DOI：10.1073/pnas.1222051110

• monocyte adhesion
• THP-1 cells
• inflammatory co-repressor
• vascular dysfunction
• endothelium

B-cell lymphoma-6 protein (Bcl-6) is a corepressor for inflammatory mediators such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and -3, which function to recruit monocytes to vascular endothelial cells upon inflammation. Poly [ADP ribose] polymerase 1 (PARP-1) is proinflammatory, in part through its binding at the Bcl-6 intron 1 to suppress Bcl-6 expression. We investigated the mechanisms by which PARP-1 dissociates from the Bcl-6 intron 1, ultimately leading to attenuation of endothelial inflammation. Analysis of the PARP-1 primary sequence suggested that phosphorylation of PARP-1 Serine 177 (Ser-177) by AMP-activated protein kinase (AMPK) is responsible for the induction of Bcl-6. Our results show that AMPK activation with treatment of 5-aminoimi-dazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators. Conversely, AMPK alpha suppression or knockdown produces the opposite effects. The results demonstrate an anti-infamatory pathway linking AMPK, PARP-1, and Bcl-6 in endothelial cells.

• 出版日期2013-2-19