Tissue iron overload and mechanisms of iron-catalyzed oxidative injury.
Tissue iron overload causes clinical syndromes that involve the heart, liver, and pancreas. While tissue iron uptake occurs by both transferrin-dependent and independent processes, tissue uptake in the iron overload syndromes occurs predominantly via transferrin-independent mechanisms. Increased redox-active iron present in hemeproteins and the cytosolic iron pool can catalyze oxidative damage to lipids, proteins, and nucleic acids, either by oxyradical dependent or independent mechanisms. Iron-catalyzed injury results in damage to cell constituents, including mitochondria, lysosomes, and the sarcolemmal membrane. These mechanisms of iron-mediated damage are involved in the pathogenesis of organ dysfunction in primary hemochromatosis, transfusion-related iron overload, ischemia-reperfusion injury, and cardiac anthracycline toxicity.
Lesnefsky
E J
EJ
Division of Cardiology, Case Western Reserve University, Cleveland VA Medical Center, OH 44106, USA.
D000818:Animals; D005609:Free Radicals; D006432:Hemochromatosis / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000633:toxicity*; D008954:Models, Biological; D010084:Oxidation-Reduction; D014168:Transferrin / Q000378:metabolism; D065227:Transfusion Reaction
D005609:Free Radicals; D014168:Transferrin; D007501:Iron