AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

B Gongol, T Marin, IC Peng, B Woo… - Proceedings of the …, 2013 - National Acad Sciences
B Gongol, T Marin, IC Peng, B Woo, M Martin, S King, W Sun, DA Johnson, S Chien…
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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-aminoimidazole-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, AMPKα suppression or knockdown produces the opposite effects. The results demonstrate an anti-infamatory pathway linking AMPK, PARP-1, and Bcl-6 in endothelial cells.
National Acad Sciences
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