| Popis: |
Cellular homeostasis depends on the structural and functional integrity of the membrane bilayer. Damage to the membrane can interfere with vital cellular processes, including signal transduction, molecular recognition, maintenance of the membrane potential, cellular metabolism and transport of molecules. Modification of the membrane bilayer by reactive oxidative species (ROS) is a major contributor to membrane damage and has been implicated in many pathological processes. In a number of diseases, injury to endothelial cells is mediated by oxidative species generated during ischemia/reperfusion or by activated neutrophils. During ischemia and oxidant injury, several metabolic events occur, including depletion of intracellular ATP and formation of a number of purine catabolites including inosine (Ino), hypoxanthine (Hyp) and adenosine (Ado) (Halliwell and Gutteridge, 1990). Accumulated Hyp can be oxidized by xanthine oxidase when the tissue is oxygenated, causing rapid generation of Superoxide and hydrogen peroxide. On the other hand, formation of Ado is especially important because it has vasodilatory and antiinflammatory activity. Alterations in nucleoside transport (NT) by ROS might have an effect on extracellular Ado concentration in vivo. Reduced Ado transport could elevate Ado concentrations, especially when Ado is formed extracellularly. Inhibition of NT could also diminish extracellular nucleoside uptake required for the reconstitution of intracellular nucleotide pools after cellular stress. Decreased nucleoside efflux might protect cells by allowing more efficient intracellular nucleoside salvage. |
