Dataset Information

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

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-?B) 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-?B targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-?) treatment. The short hairpin RNA (shRNA) against AMPK ?1 in HUVECs attenuated the adenine-induced inhibition of NF-?B activation in response to TNF-?, 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.

SUBMITTER: Cheng YF

PROVIDER: S-EPMC4636334 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Cheng Yi-Fang YF Young Guang-Huar GH Lin Jiun-Tsai JT Jang Hyun-Hwa HH Chen Chin-Chen CC Nong Jing-Yi JY Chen Po-Ku PK Kuo Cheng-Yi CY Kao Shao-Hsuan SH Liang Yao-Jen YJ Chen Han-Min HM

PloS one 20151106 11

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 ti ...[more]

PMID: 26544976

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Project description:Endothelial injury, characterized by an inflammatory response and increased permeability, is an initial stage of atherosclerosis (AS). Adenosine 5'-monophosphate (AMP), activated protein kinase (AMPK), and Nuclear Factor kappa B (NF-κB)/Yin Yang 1(YY1) signaling pathways play important roles in the process of endothelial injury. Berberine (BBR), a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including anti-inflammatory, antimicrobial, antidiabetic, anticancer, and antioxidant activities. Previous studies showed a protective effect of berberine against endothelial injury. However, the underlying mechanism remains unclear. We explored the potential effect of BBR on TNF- (tumor necrosis factor-) α-induced injury of human umbilical endothelial cells (HUVECs) and studied its possible molecular mechanism. In the present study, HUVECs were divided into three groups. HUVEC viability was measured with Cell Counting Kit-8 assay. Extracellular lactic dehydrogenase (LDH) concentration was measured with LDH leakage assay. Endothelial microparticle (EMP) numbers were evaluated by flow cytometry analysis assay. The expression of proinflammatory cytokines was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of NF-κB and YY1 was detected by Real-Time PCR (RT-PCR). The protein expression of NF-κB, YY1, and AMPK was detected by immunofluorescence microscopy assay or western blot analysis. The results showed that LDH concentration, EMPs numbers, and the expression of proinflammatory cytokines (IL-6, IL-8, and IL-1β) increased in TNF-α-induced injured HUVECs, but ameliorated by BBR pretreatment. BBR pretreatment upregulated the expression of phosphorylated AMPK and downregulated the expressions of NF-κB and YY1 in injured HUVECs induced by TNF-α, which were offset by the AMPK inhibitor Compound C (CC). The results indicated that BBR protected against TNF-α-induced endothelial injury via the AMPK/NF-κB/YY1 signaling pathway.

Dataset Information

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

Publications

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

Similar Datasets

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