Mechanically stimulated ATP release from mammalian cells: systematic review and meta-analysis

Abstract

Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a meta-analysis of 278 systematically identified studies that investigated mechanically stimulated ATP release (MSAR) to quantify the amounts, kinetics and mechanisms of ATP release under normal and pathological conditions. Mechanically stimulated mammalian cells were shown to release 38.6 [95% confidence interval (CI): 18.2-81.8] amol ATP/cell on average with a characteristic time constant of 32 s (95% CI: 16-66). Analysis of ATP release mechanisms revealed the existence of conserved and tissue-specific release routes. We assessed ATP release in pathophysiological states, and found that ATP release was elevated in inflammation and injury, and attenuated in hereditary (such as cystic fibrosis) and metabolic (such as type II diabetes) conditions. Our study links cell-specific ATP release mechanisms to pathophysiological changes in ATP release and allows ATP release-targeting interventions to be mapped to site-specific effects. This work demonstrates that quantitative synthesis of basic research can generate non-trivial hypotheses and inform evidence-driven translational studies.

P2Y13 and P2X7 receptors modulate mechanically induced adenosine triphosphate release from mast cells

“…Adenosine triphosphate plays a role of a stress‐responsive signalling molecule that is liberated from a variety of cells in response to MS [6] . Extracellular ATP (eATP) and its hydrolysed products such as adenosine diphosphate (ADP) and adenosine (Ado) participate in various physiological and pathophysiological processes by binding to their corresponding receptors [7] .…”

Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells

“…The present results report an increase in the amount of ATP release from dental epithelial cells with an miR-1 knockdown. Five groups of channels have been identified as ATP release channels, such as connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs), and maxi-anion channels (MACs) (Liu et al, 2008;Kinnamon and Finger, 2013;Mikolajewicz et al, 2018). Furthermore, the classical exocytosis and non-vesicular mechanisms of cellular ATP release have been reported in various cell types.…”

Role of UDP-Sugar Receptor P2Y14 in Murine Osteoblasts

“…The amplitude of mechanically-stimulated [Ca 2+ ] i elevations in Y14 KO C2-Ob cells was significantly higher than in Wt cells (Figure 3c,d). In addition, [Ca 2+ ] i responses in neighbouring non-stimulated C2-Ob cells, which are mediated by ATP and ADP released from the mechanically-stimulated cell [19,20,59], tended to have more oscillatory peaks (p = 0.09) with greater magnitudes (p = 0.09) (Figure 3e-g). When ATP and ADP were applied directly to Fura2-loaded Wt or Y14 KO cells, calcium responses to both agonists were significantly potentiated in Y14 KO cultures ( Figure 3h).…”

“…The lack of discernable dose-dependency that accompanied the potentiated UDPG-induced [Ca 2+ ] i elevations in P2Y 14 -inhibited osteoblasts prompted us to investigate whether P2Y 14 inhibition affects cellular sensitivity to mechanical stimulation that is known to induce purinergic signalling in bone cells [19]. We mechanically-stimulated osteoblasts by dispensing 10% media volume into Fura2-loaded osteoblast cultures (Figure 3a).…”

“…In bone, mechanical loading leads to the rapid release of extracellular nucleotides through vesicular and conductive pathways [19], as well as through reversible membrane disruption [20], thereby positioning P2 receptor signalling upstream of the mechano-adaptive skeletal response. In vitro studies have demonstrated that certain P2 receptors promote anabolic responses in osteoblasts (e.g., P2X 5 [21], P2Y 1 [22][23][24][25], P2Y 12 [26,27], P2Y 13 [28,29]) while others have catabolic effects through increased osteoclast activity (e.g., P2X 2 [30], P2X 4 [31][32][33], P2X 5 [34], P2X 7 [35][36][37][38]), thereby framing the P2 receptor family as a complex signalling network in the skeletal system.…”