title: AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6.
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.
authors: Biochemistry and Molecular Biology Graduate Program, and Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.
authors: Brendan
authors: B
authors: Gongol
authors: Traci
authors: T
authors: Marin
authors: I-Chen
authors: IC
authors: Peng
authors: Brian
authors: B
authors: Woo
authors: Marcy
authors: M
authors: Martin
authors: Stephanie
authors: S
authors: King
authors: Wei
authors: W
authors: Sun
authors: David A
authors: DA
authors: Johnson
authors: Shu
authors: S
authors: Chien
authors: John Y-J
authors: JY
authors: Shyy
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D007438:Introns; D051379:Mice; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D051560:Proto-Oncogene Proteins c-bcl-6; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases
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