Purinergic signaling in the modulation of redox biology

Abstract

Purinergic signaling is a cell communication pathway mediated by extracellular nucleotides and nucleosides. Tri- and diphosphonucleotides are released in physiological and pathological circumstances activating purinergic type 2 receptors (P2 receptors): P2X ion channels and P2Y G protein-coupled receptors. The activation of these receptors triggers the production of reactive oxygen and nitrogen species and alters antioxidant defenses, modulating the redox biology of cells. The activation of P2 receptors is controlled by ecto-enzymes named ectonucleotidases, E-NTPDase1/CD39 and ecto-5’-nucleotidase/CD73) being the most relevant. The first enzyme hydrolyzes adenosine triphosphate (ATP) and adenosine diphosphate (ADP) into adenosine monophosphate (AMP), and the second catalyzes the hydrolysis of AMP to adenosine. The activity of these enzymes is diminished by oxidative stress. Adenosine actives P1 G-coupled receptors that, in general, promote the maintenance of redox hemostasis by decreasing reactive oxygen species (ROS) production and increase antioxidant enzymes. Intracellular purine metabolism can also contribute to ROS generation via xanthine oxidase activity, which converts hypoxanthine into xanthine, and finally, uric acid. In this review, we describe the mechanisms of redox biology modulated by purinergic signaling and how this signaling may be affected by disturbances in the redox homeostasis of cells.

Reactive oxygen species–dependent upregulation of death receptor, tumor necrosis factor receptor 1, is responsible for theophylline-mediated cytotoxicity in MDA-MB-231 breast cancer cells

“…Studies have shown theophylline and adenosine to compete for adenosine receptor when given in combination [29]. It is also known that activation of adenosine receptor after binding with adenosine reduces ROS [30,31]. In this context, we studied the levels of ROS after treatment with theophylline and adenosine (200 µmol/l).…”

Temperature-Related Effects of Myocardial Protection Strategies in Swine Hearts after Prolonged Warm Ischemia

“…The nucleoside adenosine is a metabolite that elicits coronary vasodilation. Furthermore, it was demonstrated that in hypoxic conditions, under energy depletion, cellular levels of adenosine increase, eliciting an antioxidant activity by inducing antioxidant enzymes activity [50,51]. As a result, adenosine has been extensively investigated for its cardioprotective effects, with controversial results in-vivo.…”

Damage-associated molecular patterns in vitiligo: igniter fuse from oxidative stress to melanocyte loss

“…Also, ATP directly activates the plasma membrane channel P2X7 receptor (P2X7R), leading to an intracellular influx of potassium ions, key triggers which activate the NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome. Simultaneously in the mitochondria, ROS and ATP production are coupled to regulate cellular redox reactions [ 57 ]. In healthy tissue stroma, levels of ATP and its metabolite adenosine are negligible, while their accumulation is significantly increased in inflammatory or tumor microenvironments [ 58 ].…”