The Role of Extracellular Adenosine Triphosphate in Ischemic Organ Injury

Abstract

In this review, we aim to discuss the molecular mechanisms behind adenosine triphosphate-mediated ischemic tissue injury and evaluate the role of extracellular adenosine triphosphate in ischemic injury in specific organs, in order to provide a greater understanding of the pathophysiology of this complex process. We also appraise potential future therapeutic strategies to limit damage in various organs, including the heart, brain, kidneys, and lungs.

Innate immune responses to trauma

“…1), in an attempt to clear damaged tissues, that is followed by the activation of repair mechanisms, with the ultimate goal of restoring cells and tissues to their pre-injury state 11,12 . Severe injury can be associated with the presence of ‘non-self’ pathogen-associated molecular patterns (PAMPs) from infectious agents (bacteria, viruses and fungi), along with the release of large amounts of ‘self’ damage-associated molecular patterns (DAMPs) such as ATP, HMGB-1, matricryptins, cold-inducible RNA-binding protein, histones and mitochondrial DNA 13–17 .…”

Thymosin beta 4 treatment improves left ventricular function after myocardial infarction and is related to Up-regulation of chitinase 3-like-1 in mice

“…In the heart ATP acts mainly on P 2 -receptors causing vasoconstriction and increased inotropy, but can also induce arrhythmias. ATP is a powerful chemoattractant for leukocytes and signaling through P 2x7 -receptors induces inflammatory and apoptotic pathways [20]. In order to control ATP-mediated signaling, ATP is metabolized to ADP and further to AMP by different hydrolyzing enzymes, collectively called ATPases and ADPases.…”

Extracellular nucleotide signaling in solid organ transplantation

“…Although reperfusion (the reintroduction of oxygenated blood to the organ or tissue) induces inflammation and injury, it is necessary for organ viability. Cellular injury that occurs during ischemia results in the release of ATP into the local extracellular environment, which is further exacerbated during reperfusion, where sudden reoxygenation and resulting production of reactive oxygen species cause further release of DAMPs including ATP . Although the length of ischemic organ preservation time is minimized to reduce damage at the time of engraftment, IRI has been shown to affect both acute and chronic graft survival …”

“…Cellular injury that occurs during ischemia results in the release of ATP into the local extracellular environment, which is further exacerbated during reperfusion, where sudden reoxygenation and resulting production of reactive oxygen species cause further release of DAMPs including ATP. [8][9][10][11] Although the length of ischemic organ preservation time is minimized to reduce damage at the time of engraftment, IRI has been shown to affect both acute and chronic graft survival. 12,13 A number of recent studies have established that extracellular ATP accumulation and subsequent purinergic signaling are an important mediator of solid organ transplantation.…”