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Cited by 121Metabolism, Diabetes, and CancerNF-κB Signaling PathwaysAtherosclerosis and Cardiovascular Diseases

AMP-activated protein kinase suppresses endothelial cell inflammation through phosphorylation of transcriptional coactivator p300

Zhang, Yuan, Qiu, Jian, Wang, Xiaoming, Zhang, Yuhua, Xia, Min·2011·Arteriosclerosis Thrombosis and Vascular Biology
DOI 10.1161/atvbaha.111.237453
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Abstract

OBJECTIVE: Considerable evidence supports the early involvement of monocyte/macrophage recruitment to activated endothelial cells by leukocyte adhesion molecules during atherogenesis. AMP-activated protein kinase (AMPK) is highly expressed in vascular endothelial cells, but its impact on monocyte adhesion and the related mechanisms are not fully understood. The present study was designed to evaluate the impact of and gain mechanistic insight into the signaling coupling AMPK function to the antiinflammatory response. METHODS AND RESULTS: 5-Aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) treatment or overexpression of constitutively active AMPK markedly reduced human monocytic human acute monocytic leukemia cell line-1 cell adhesion and the expression of vascular cell adhesion molecule-1 in tumor necrosis factor-α-activated human aortic endothelial cells. Furthermore, AICAR or constitutively active AMPK overexpression strongly inhibited the histone acetyltransferase activity of the transcriptional coactivator p300 by phosphorylation of Ser89, which in turn decreased tumor necrosis factor-α-activated p300-mediated acetylation of nuclear factor-κB p65 on Lys221 and reduced the DNA binding activity of nuclear factor-κB by inhibiting its recruitment to its target gene promoters. AMPK phosphorylates the transcriptional coactivator p300 via the atypical protein kinase Cι/λ. CONCLUSIONS: Our findings demonstrate that transcriptional coactivator p300 phosphorylation at Ser89 by AMPK is critical for the therapeutic effect of AMPK and may be a potential target for pharmaceutical intervention in inflammatory diseases such as atherosclerosis.

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Crossref · 10.1161/atvbaha.111.237453

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48 of 48 references verified0 citation errors · 0 not checkable

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  • AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways.

    “Indeed, studies have uncovered that AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants [248,249,252,253] by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways [254,255,256].”

    From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [249]

  • AICAR plays anti-inflammatory roles in vascular cells both in vitro and in vivo.

    “Additionally, AICAR, an AMPK activator, plays anti-inflammatory roles in vascular cells both in vitro and in vivo [248,249,250].”

    From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [249]

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Authors
Zhang, Y., Qiu, J., Wang, X., Zhang, Y., & Xia, M.
Affiliations
Sun Yat-sen University (CN)
ORCID
Venue
Arteriosclerosis Thrombosis and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-12
Volume
31
Issue
12
Pages
2897-2908
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.111.237453
OpenAlex
W2105082599
Cited by
121
References
48
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 9 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 12 · 2017: 12 · 2016: 11 · 2015: 13 · 2014: 6 · 2013: 11 · 2012: 6
FWCI
2.98
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
AMPK, P300, endothelial inflammation, monocyte adhesion, VCAM-1, NF-κB p65 acetylation, histone acetyltransferase, atherosclerosis, anti-inflammatory signaling, AICAR
MeSH terms
Aminoimidazole Carboxamide, Aorta, Cell Adhesion, Cells, Cultured, Endothelium, Vascular, Gene Expression Regulation, Humans, Inflammation, Monocytes, Phosphorylation, Protein Kinase C, Ribonucleotides, NF-kappa B, Vascular Cell Adhesion Molecule-1, E1A-Associated p300 Protein, Histone Acetyltransferases, AMP-Activated Protein Kinases

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