Control of Adenosine Transport by Hypoxia

Görlach, Agnes

doi:10.1161/01.res.0000174112.36064.77

Cited by 53 publications

(40 citation statements)

References 30 publications

(32 reference statements)

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“…According to a previously proposed model [2], inflammatory damage to blood vessels induces low oxygen supply and hypoxiadriven increase of extracellular adenosine which accumulates because of altered expression of several key enzymes involved in the adenosine triphosphate (ATP) metabolism [3]. Adenosine, an endogenous purine nucleoside that is produced intra-or extracellularly by injured tissue cells, binds to four types of receptor, namely A 1 , A 2A , A 2B and A 3 , which are members of the G protein-coupled family of receptors [4].…”

Section: Introductionmentioning

confidence: 99%

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Jacquin

Franceschi

et al. 2012

Purinergic Signalling

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We examined the short-course expression of various parameters involved in the adenosinergic signalling of a human T cell line during in vitro decrease of the medium culture oxygen tension mimicking in vivo hypoxia. Fall of 92 mmHg in oxygen tension of culture medium induced in CEM, a CD4+ human T cell line, a continuous production of hypoxia-inducing factor-1α with a plateau value at 9 h, a rapid increase in adenosine production peaking at 3 h and a decrease in adenosine deaminase peaking at 6 h. The adenosine A 2A receptor (A 2A R) protein level of CEM cells was enhanced with a peak at 6 h. Intracellular 3′,5′-cyclic adenosine monophosphate accumulated in CEM cells with a maximal level at 9 h. These results show that a humancultured T cells line can upregulate its own adenosine production and A 2A R expression during exposure to acute hypoxia. Hypoxia-increased stimulation of the adenosinergic signalling of T cells may have immunosuppressive properties and, consequently, A 2A R agonists may have therapeutic relevance.

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Section: Introductionmentioning

confidence: 99%

Fall in oxygen tension of culture medium stimulates the adenosinergic signalling of a human T cell line

Jacquin

Franceschi

et al. 2012

Purinergic Signalling

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“…Adenosine is an endogenous purine nucleoside and hypoxia can induce adenosine accumulation in the extracellular environment mainly through regulation of cellular metabolism. 13 By interacting with G-protein-coupled receptors, adenosine can exert substantial immunosuppressive effects. 14,15 There are currently four clearly defined AR subtypes:…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A2

et al. 2009

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Hypoxia is a major characteristic of the tumor microenvironment, and its effects on immune cells are proposed to be important factors for the process of tumor immune escape. It has been reported that hypoxia affects the function of dendritic cells and the antitumor function of T cells. Here we discuss the effects of hypoxia on T-cell survival. Our results showed that hypoxia induced apoptosis of T cells. Adenosine and adenosine receptors (AR) are important to the hypoxia-related signaling pathway. Using AR agonists and antagonists, we demonstrated that hypoxia-induced apoptosis of T cells was mediated by A 2a and A 2b receptors. Furthermore, we are the first, to our knowledge, to report that hypoxia significantly inhibited the expression of chemokine C receptor 7 (CCR7) of T cells via the A 2 R signal pathway, perhaps representing a mechanism of hypoxia-induced apoptosis of T cells. Collectively, our research demonstrated that hypoxia induces T-cell apoptosis by the A 2 R signaling pathway partly by suppressing CCR7. Blocking the A 2 R signaling pathway and/or activation of CCR7 can increase the anti-apoptosis function of T cells and may become a new strategy to improve antitumor potential.

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“…It is a ubiquitously produced by stepwise dephosphorylation of ATP. Extracellular adenosine acts as a signaling molecule which mediates a number of physiological and metabolic effects (Gorlach, 2005). Adenosine accumulation during ischemia and inflammation protects tissue from injury ).…”

Section: Adenosine and Its Receptorsmentioning

confidence: 99%

“…Some effects of adenosine which are considered tissue or cytoprotective are mediated by a variety of cellular mechanisms. These include stimulation of glycogen breakdown to provide glucose for ATP production via anaerobic glycolysis, reduction in neuronal excitability as well as neurotransmitter release to reduce neuronal energy demands (Gorlach, 2005), increasing the ratio of oxygen supply to demand by causing vasodilation, reducing inflammation and promoting angiogenesis (Adair, 2005;Jacobson and Gao, 2006). The idea that adenosine has an important role in cardiovascular function was first introduced more than 80 years ago when Drury and Szent-Gyorgyi (1929) found that extracts from heart and other tissues produced vasodilation, hypotension, bradycardia, and a decrease in atrioventricular conduction velocity.…”

Section: Adenosine and Its Receptorsmentioning

confidence: 99%

“…It is generated and metabolized through stepwise dephosphorylation of ATP (Figure 1). ATP and ADP are converted by CD39 (ecto-ATP apyrase) to AMP through a process activated by hypoxia (Gorlach, 2005). Dephosphorylation of AMP is mediated intracellularly by cytosolic-5′-nucleotidase and extracellularly by membrane-bound ecto-5′-nucleotidase (CD73), respectively.…”

Section: Adenosine: Formation and Metabolismmentioning

confidence: 99%

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