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

Gongol, Brendan; Marin, Traci; Peng, I‐Chen; Woo, Brian; Martin, Marcy; King, Stephanie J.; Sun, Wei; Johnson, David A.; Chien, Shu; Shyy, John Y.‐J.

doi:10.1073/pnas.1222051110

Cited by 60 publications

(77 citation statements)

References 48 publications

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“…For example, CTCF (CCCTC-binding factor) promotes PARP-1–mediated PARylation and inhibition of DNMT1 (16) to preserve the DNA methylation status, particularly at unmethylated regions of daughter cells (16, 27). This cascade may be governed by AMPK (8). We demonstrated here that AMPK decreased DNMT1 activity at 30 min (Fig.…”

Section: Discussionmentioning

confidence: 99%

AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1

et al. 2017

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Adenosine monophosphate (AMP)–activated protein kinase (AMPK) acts as a master regulator of cellular energy homeostasis by directly phosphorylating metabolic enzymes and nutrient transporters and by indirectly promoting the transactivation of nuclear genes involved in mitochondrial biogenesis and function. We explored the mechanism of AMPK-mediated induction of gene expression. We identified AMPK consensus phosphorylation sequences in three proteins involved in nucleosome remodeling: DNA methyltransferase 1 (DNMT1), retinoblastoma binding protein 7 (RBBP7), and histone acetyltransferase 1 (HAT1). DNMT1 mediates DNA methylation that limits transcription factor access to promoters and is inhibited by RBBP7. Acetylation of histones by HAT1 creates a more relaxed chromatin-DNA structure that favors transcription. AMPK-mediated phosphorylation resulted in the activation of HAT1 and inhibition of DNMT1. For DNMT1, this inhibition was both a direct effect of phosphorylation and the result of increased interaction with RBBP7. In human umbilical vein cells, pharmacological AMPK activation or pulsatile shear stress triggered nucleosome remodeling and decreased cytosine methylation, leading to increased expression of nuclear genes encoding factors involved in mitochondrial biogenesis and function, such as peroxisome proliferator–activated receptor gamma coactivator–1α (PGC-1α), transcription factor A (Tfam), and uncoupling proteins 2 and 3 (UCP2 and UCP3). Similar effects were seen in the aortas of mice given pharmacological AMPK activators, and these effects required AMPK2α. These results enhance our understanding of AMPK-mediated mitochondrial gene expression through nucleosome remodeling.

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Section: Discussionmentioning

confidence: 99%

AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1

et al. 2017

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“…Such repression of MCP-1 by sustained LSS may be due to the eNOS expression and NO production that inhibit protein kinase C (PKC)-ε and ERK 1/2 62 . Furthermore, prolonged PSS induces the AMPK / poly [ADP ribose] polymerase 1(PARP-1) / B-cell lymphoma-6 (Bcl-6) pathway to inhibit expressions of VCAM-1, MCP-1, and MCP-3 63 . The Tie family of receptor tyrosine kinases (RTK) has been shown to contribute to the pro-inflammatory endothelial phenotype, as indicated by the findings that depletion of Tie1 augments the LSS-induced simulation of eNOS and -inhibitions of kappa B (I-κB) activity and ICAM-1 expression 64 .…”

Section: Shear Stress-induced Signal Transduction Gene Expressionmentioning

confidence: 99%

Shear Stress–Initiated Signaling and Its Regulation of Endothelial Function

Zhou

Chien

2014

ATVB

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Atherosclerosis develops preferentially at branches and curvatures of the arterial tree, where blood flow pattern is disturbed rather than being laminar, and wall shear stress has an irregular distribution without defined directions. The endothelium in the atherosusceptible regions, in comparison to that in atheroresistant regions, shows activation of pro-proliferative and pro-inflammatory gene expressions, reduced production of nitric oxide (NO), increased leukocyte adhesion and permeability, as well as other atheroprone phenotypes. Differences in gene expressions and cell phenotypes have been detected in endothelia residing in native atherosusceptible and atheroresistant regions of the arteries, or in arteries from animal models with artificial creation of disturbed flow. Similar results have also been shown in in vitro systems that apply controlled shear stresses with or without clear directions to cultured endothelial cells (ECs) in fluid-dynamically designed flow-loading devices. The available evidence indicates that the coordination of multiple signaling networks, rather than individual separate pathways, link the mechanical signals to specific genetic circuitries in orchestrating the mechanoresponsive networks to evoke comprehensive genetic and functional responses.

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“…Indeed, reduced atherosclerotic plaque formation was reported in AMPKα1 −/− /ApoE −/− [168], while it increased in AMPKα2−/−/LDLR−/− mice [166]. One of the substrates of AMPKa2 is poly [ADP ribose] polymerase 1 (PARP1) [169]. Originally, PARP1 was recognized as the molecule that utilized NAD + to synthesize poly(ADP)-ribose (PAR) and “PARylated” itself and other nuclear proteins [170].…”

Section: Other Sumoylation Events Which Are Crucial For Regulating Ementioning

confidence: 99%

Flow signaling and atherosclerosis

Sandhu

Quintana-Quezada

et al. 2016

Cell. Mol. Life Sci.

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Atherosclerosis rarely develops in the region of arteries exposed to undisturbed flow (u-flow, unidirectional flow). Instead, atherogenesis occurs in the area exposed to disturbed flow (d-flow, multidirectional flow). Based on these general pathohistological observations, u-flow is considered to be atheroprotective, while d-flow is atherogenic. The fact that u-flow and d-flow induce such clearly different biological responses in the wall of large arteries indicates that these two types of flow activate each distinct intracellular signaling cascade in vascular endothelial cells (ECs), which are directly exposed to blood flow. The ability of ECs to differentially respond to the two types of flow provides an opportunity to identify molecular events that lead to endothelial dysfunction and atherosclerosis. In this review, we will focus on various molecular events, which are differentially regulated by these two flow types. We will discuss how various kinases, ER stress, inflammasome, SUMOylation, and DNA methylation play roles in the differential flow response, endothelial dysfunction, and atherosclerosis. We will also discuss the interplay among the molecular events and how they coordinately regulate flow-dependent signaling and cellular responses. It is hoped that clear understanding of the way how the two flow types beget each unique phenotype in ECs will lead us to possible points of intervention against endothelial dysfunction and cardiovascular diseases.

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

Cited by 60 publications

References 48 publications

AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1

AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1

Shear Stress–Initiated Signaling and Its Regulation of Endothelial Function

Flow signaling and atherosclerosis

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