移植技術と研究

Intracellular Signaling in Ischemia/Reperfusion Injury (IRI): From Mechanistic Insights to Therapeutic Options

Abstract

Muhamad Imtiaz Ashraf, Marion Enthammer, Martina Haller, Katarzyna Koziel, Martin Hermann and Jakob Troppmair

Transplantation of solid organs is invariably linked to a disruption of oxygen and nutrient supply. Damage initiated in the ischemic period is greatly enhanced during reperfusion. In particular the excessive production of reactive oxygen species (ROS) plays a key role in the development of ischemia/reperfusion injury (IRI), which in the clinical setting is difficult to control through the use of antioxidants. Ischemia/reperfusion (IR) is also marked by the activation of intracellular signaling pathways, which may have protective but also damaging effects. Modulating intracellular signaling thus may hold the promise to prevent or minimize IRI. Most intriguingly, some of these pathways have been shown recently to control mitochondrial events, including the production of ROS. Understanding this cytoplasmic/ mitochondrial crosstalk will be the basis for the development of novel approaches for the prevention of IRI.