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Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3161-6. doi: 10.1073/pnas.1222051110. Epub 2013 Feb 4.

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

Author information

1
Biochemistry and Molecular Biology Graduate Program, and Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.

Abstract

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.

PMID:
23382195
PMCID:
PMC3581905
DOI:
10.1073/pnas.1222051110
[Indexed for MEDLINE]
Free PMC Article

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