Interaction of reactive oxygen species with ion transport mechanisms.
The use of electrophysiological and molecular biology techniques has shed light on reactive oxygen species (ROS)-induced impairment of surface and internal membranes that control cellular signaling. These deleterious effects of ROS are due to their interaction with various ion transport proteins underlying the transmembrane signal transduction, namely, 1) ion channels, such as Ca2+ channels (including voltage-sensitive L-type Ca2+ currents, dihydropyridine receptor voltage sensors, ryanodine receptor Ca2+-release channels, and D-myo-inositol 1,4,5-trisphosphate receptor Ca2+-release channels), K+ channels (such as Ca2+-activated K+ channels, inward and outward K+ currents, and ATP-sensitive K+ channels), Na+ channels, and Cl- channels; 2) ion pumps, such as sarcoplasmic reticulum and sarcolemmal Ca2+ pumps, Na+-K+-ATPase (Na+ pump), and H+-ATPase (H+ pump); 3) ion exchangers such as the Na+/Ca2+ exchanger and Na+/H+ exchanger; and 4) ion cotransporters such as K+-Cl-, Na+-K+-Cl-, and Pi-Na+ cotransporters. The mechanism of ROS-induced modifications in ion transport pathways involves 1) oxidation of sulfhydryl groups located on the ion transport proteins, 2) peroxidation of membrane phospholipids, and 3) inhibition of membrane-bound regulatory enzymes and modification of the oxidative phosphorylation and ATP levels. Alterations in the ion transport mechanisms lead to changes in a second messenger system, primarily Ca2+ homeostasis, which further augment the abnormal electrical activity and distortion of signal transduction, causing cell dysfunction, which underlies pathological conditions.
Kourie
J I
JI
Membrane Transport Group, Department of Chemistry, The Faculties, The Australian National University, Canberra, Australian Capital Territory 0200, Australia.
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D015227:Lipid Peroxidation; D015221:Potassium Channels / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D000252:Calcium-Transporting ATPases