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PLoS One. 2015 Nov 6;10(11):e0142283. doi: 10.1371/journal.pone.0142283. eCollection 2015.

Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

Author information

1
Energenesis Biomedical Co., Ltd., New Taipei City, Taiwan.
2
Department of Life Science, Institute of Applied Science and Engineering, Catholic Fu-Jen University, New Taipei City, Taiwan.
3
Department of Internal Medicine, Collage of Medicine, National Taiwan University, Taipei, Taiwan.
4
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.

Abstract

The AMP-activated protein kinase (AMPK) signaling system plays a key role in cellular stress by repressing the inflammatory responses induced by the nuclear factor-kappa B (NF-κB) system. Previous studies suggest that the anti-inflammatory role of AMPK involves activation by adenine, but the mechanism that allows adenine to produce these effects has not yet been elucidated. In human umbilical vein endothelial cells (HUVECs), adenine was observed to induce the phosphorylation of AMPK in both a time- and dose-dependent manner as well as its downstream target acetyl Co-A carboxylase (ACC). Adenine also attenuated NF-κB targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-α) treatment. The short hairpin RNA (shRNA) against AMPK α1 in HUVECs attenuated the adenine-induced inhibition of NF-κB activation in response to TNF-α, thereby suggesting that the anti-inflammatory role of adenine is mediated by AMPK. Following the knockdown of adenosyl phosphoribosyl transferase (APRT) in HUVECs, adenine supplementation failed to induce the phosphorylation of AMPK and ACC. Similarly, the expression of a shRNA against APRT nullified the anti-inflammatory effects of adenine in HUVECs. These results suggested that the role of adenine as an AMPK activator is related to catabolism by APRT, which increases the cellular AMP levels to activate AMPK.

PMID:
26544976
PMCID:
PMC4636334
DOI:
10.1371/journal.pone.0142283
[Indexed for MEDLINE]
Free PMC Article

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