Extracellular adenosine activates AMP-dependent protein kinase (AMPK)

Aymerich, Ivette; Foufelle, Fabienne; Ferré, Pascal; Casado, F. Javier; Pastor‐Anglada, Marçal

doi:10.1242/jcs.02865

Cited by 90 publications

(86 citation statements)

References 49 publications

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“…A well documented intracellular effect of adenosine is the activation of AMPK [27] 11 and our results show that activation of AMPK reduces SERT activity. This result indicates the possibility of SERT regulation mediated by intracellular adenosine and AMPK.…”

Section: Discussionsupporting

confidence: 61%

“…Cells were treated for 1 day with AICAR, a known pharmacological activator of AMPK [27]. The results showed that AMPK activation reduced SERT activity; however, this effect was additive to the inhibition yielded by adenosine treatment (Fig.…”

Section: Page 9 Of 27mentioning

confidence: 93%

“…A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 9 The intracellular adenosine has been shown to activate AMP activated kinase (AMPK) [27], therefore, the role of AMPK on adenosine effect on SERT was assessed. Cells were treated for 1 day with AICAR, a known pharmacological activator of AMPK [27].…”

Section: Page 9 Of 27mentioning

confidence: 99%

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Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Matheus¹,

Mendoza²,

Iceta³

et al. 2009

Biochemical Pharmacology

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Serotonin plays a critical role in the regulation of intestinal physiology. The serotonin transporter (SERT) expressed in the intestinal epithelium determines 5-HT availability and activity. The serotoninergic system and SERT activity have been described as being altered in chronic intestinal pathologies such as inflammatory diseases. Adenosine has also been shown to be involved in a variety of intestinal functions and to play a central role in the regulation of inflammatory responses of injured tissue. Since the modulation of SERT by adenosine in the intestine remains unknown, the aim of the present work was to study the effect of adenosine on SERT activity and expression and to determine the molecular mechanism involved. The study has been carried out using human enterocyte-like Caco-2 cells which endogenously express SERT. The results show that adenosine diminishes SERT activity in both the apical and basal membranes by acting in the intrinsic molecule with no alteration of either SERT mRNA or protein levels. The effect of adenosine appears to be mediated by A 2 receptors and activation of the cAMP/PKA signalling pathway. Moreover, the adenosine effect did not seem to involve the activation of AMP activated protein kinase. Adenosine effects are reached at high concentrations, which suggests that adenosine modulation of SERT may be significant under conditions of inflammation and tissue injury.

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Section: Discussionsupporting

confidence: 61%

Section: Page 9 Of 27mentioning

confidence: 93%

Section: Page 9 Of 27mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Matheus¹,

Mendoza²,

Iceta³

et al. 2009

Biochemical Pharmacology

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show abstract

“…Previously, adenosine has been reported to be an effective activator of AMPK (17). As cordycepin is a structural analogue of adenosine, it is reasonable to speculate that it is also an AMPK activator.…”

Section: Discussionmentioning

confidence: 99%

Cordycepin Prevents Hyperlipidemia in Hamsters Fed a High-Fat Diet via Activation of AMP-Activated Protein Kinase

et al. 2010

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“…Interestingly, short-term (1-10 minutes) incubation of human endothelial cells (38) as well as rat liver and intestinal epithelial cells (39) with micromolar concentrations of adenosine or its precursor nucleotides triggered a transient activation of AMPK. However, the mechanisms of these acute effects may differ substantially from the chronic effects of adenosine on AMPK inhibition seen in our experimental settings.…”

Section: Discussionmentioning

confidence: 99%

Adenosine Inhibits Tumor Cell Invasion via Receptor-Independent Mechanisms

Virtanen

Kukkonen-Macchi

Vainio

et al. 2014

Molecular Cancer Research

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Extracellular adenosine mediates diverse anti-inflammatory, angiogenic, and other signaling effects via binding to adenosine receptors, and it also regulates cell proliferation and death via activation of the intrinsic signaling pathways. Given the emerging role of adenosine and other purines in tumor growth and metastasis, this study evaluated the effects of adenosine on the invasion of metastatic prostate and breast cancer cells. Treatment with low micromolar concentrations of adenosine, but not other nucleosides or adenosine receptor agonists, inhibited subsequent cell invasion and migration through Matrigel-and laminin-coated inserts. These inhibitory effects occurred via intrinsic receptor-independent mechanisms, despite the abundant expression of A2B adenosine receptors (ADORA2B). Extracellular nucleotides and adenosine were shown to be rapidly metabolized on tumor cell surfaces via sequential ecto-5 0 -nucleotidase (CD73/NT5E) and adenosine deaminase reactions with subsequent cellular uptake of nucleoside metabolites and their intracellular interconversion into ADP/ATP. This was accompanied by concurrent inhibition of AMP-activated protein kinase and other signaling pathways. No differences in the proliferation rates, cytoskeleton assembly, expression of major adhesion molecules [integrin1b (ITGB1), CD44, focal adhesion kinase], and secretion of matrix metalloproteinases were detected between the control and treated cells, thus excluding the contribution of these components of invasion cascade to the inhibitory effects of adenosine. These data provide a novel insight into the ability of adenosine to dampen immune responses and prevent tumor invasion via two different, adenosine receptor-dependent and -independent mechanisms.Implications: This study suggests that the combined targeting of adenosine receptors and modulation of intracellular purine levels can affect tumor growth and metastasis phenotypes.

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Extracellular adenosine activates AMP-dependent protein kinase (AMPK)

Cited by 90 publications

References 49 publications

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells

Cordycepin Prevents Hyperlipidemia in Hamsters Fed a High-Fat Diet via Activation of AMP-Activated Protein Kinase

Adenosine Inhibits Tumor Cell Invasion via Receptor-Independent Mechanisms

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