2015
DOI: 10.1371/journal.pone.0142283
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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-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-de… Show more

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Cited by 22 publications
(22 citation statements)
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“…These factors serve a key role in inflammatory disease development. Activated AMPK has been reported to inhibit the inflammation reaction (45,46). The present study demonstrated that DEX affected the expression of P-AMPK in the cortex of MCAO rats in a dose-dependent manner, as illustrated in Fig.…”
Section: Discussionsupporting
confidence: 69%
“…These factors serve a key role in inflammatory disease development. Activated AMPK has been reported to inhibit the inflammation reaction (45,46). The present study demonstrated that DEX affected the expression of P-AMPK in the cortex of MCAO rats in a dose-dependent manner, as illustrated in Fig.…”
Section: Discussionsupporting
confidence: 69%
“…This may lead us to expect that its activity, along with adenine availability, is possibly related to AMPK activation and functions. In fact, it has been demonstrated that in human vascular endothelial cells, the anti‐inflammatory effect of adenine is mediated by its APRT‐catalysed conversion into AMP and the subsequent activation of AMPK . The same observation has been reported for murine microglial cells .…”
Section: Enzymes Participating In Adenylate Metabolismsupporting
confidence: 59%
“…In contrast, supplementing the diet of adult APRT mutants with adenine, restored the AMP : ATP ratio to that of control flies and abolished the effect on longevity. As the authors note, these results are counterintuitive to the mutations, and are in direct contrast to the results obtained in human cell models . Although, as assessed in the section on ADSL and AdSS, this surprising result might be explained by assuming a peculiar adenine nucleotide metabolism in Drosophila , it is impossible to apply these results to the set‐up of potential therapeutic and dietary interventions that may extend the lifespan and improve the health span of humans.…”
Section: Enzymes Participating In Adenylate Metabolismmentioning
confidence: 81%
“…Adenine can be irreversibly converted into AMP which in turn could lead to activation of AMPK which modulates inflammatory responses [ 32 ]. AMPK is activated by both AMP and phosphorylation on Thr172 of α subunit by upstream kinases.…”
Section: Resultsmentioning
confidence: 99%
“…AMPK is activated by both AMP and phosphorylation on Thr172 of α subunit by upstream kinases. Previous finding has suggested that adenine activates AMPK thereby inhibiting TNF-α signaling in HUVECs and glucose uptake in NIH-3T3 cells [ 32 33 ]. Hence we examined the effect of adenine on cellular AMP level and AMPK phosphorylation in RAW264.7 cells.…”
Section: Resultsmentioning
confidence: 99%