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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Susceptibility to oxidative stress is increased in erythrocytes of patients with beta-thalassaemia due to the free alpha-chain pool and to the excess of iron. We have investigated the effect of L-propionylcarnitine concentrations on oxidative stress determined by lactoperoxidase-hydrogen peroxide-iodide and by xanthine oxidase-acetaldehyde on erythrocytes of patients with beta-thalassaemia (major and intermedia). L-propionyl carnitine protects the erythrocytes from oxidative stress as measured by cell lysis. The protection is concentration-dependent. L-propionyl carnitine also stabilizes the cell membranes in which a latent peroxidative damage has been produced. These data suggest that L-propionyl carnitine may prove beneficial in protecting in vivo patients in which peroxidative damage of cell structure is increased as in the case of beta-thalassaemic patients.
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PMID:Protection of beta-thalassaemic erythrocytes from oxidative stress by propionyl carnitine. 785 33

Two major causes of the anemia in beta-thalassemia are a deficiency in hemoglobin (Hb) beta-subunit (and consequently HbA) synthesis and, due to the resulting excess of Hb alpha-subunits, erythroid cell hemolysis. The hemolytic component might be ameliorated by increasing the intracellular proteolysis of the excess alpha-subunits. Isolated 3H-labeled alpha-chains are known to be degraded primarily by the adenosine triphosphate (ATP)- and ubiquitin (Ub)-dependent proteolysis pathway in unfractionated beta-thalassemic hemolysates. Our objective was to increase this degradation by targeted intervention. Ub aldehyde (Ubal), a synthetic inhibitor of isopeptidases (proteases that hydrolyze the bond between the Ub polypeptide and its protein adduct), was added to reaction mixtures containing a hemolysate from the blood cells of one of four beta-thalassemic donors and 3H-alpha-chains or 3H-alpha-globin as a substrate. Optimum enhancement of ATP-dependent degradation occurred at 0.4 to 1.5 micromol/L Ubal and ranged from 29% to 115% for 3H-alpha-chains and 47% to 96% for 3H-alpha-globin among the four hemolysates. We suggest that Ubal stimulates 3H-alpha-subunit proteolysis by inhibition of an isopeptidase(s) that deubiquitinates, or "edits," Ub-3H-alpha-subunit conjugates, intermediates in the degradative pathway. In control studies, similarly low Ubal concentrations did not enhance the degradation of 3H-alpha2beta2 (HbA) tetramers or inhibit the activities of methemoglobin reductase and four selected glycolysis pathway enzymes. These and other results may be the basis for a therapeutic approach to beta-thalassemia.
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PMID:Ubiquitin aldehyde increases adenosine triphosphate-dependent proteolysis of hemoglobin alpha-subunits in beta-thalassemic hemolysates. 924 65

Iron is an essential mineral for normal cellular physiology, but an excess can result in cell injury. Iron in low-molecular-weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates; the result is wide-ranging impairment in cellular function and integrity. The rate of free radical production must overwhelm the cytoprotective defenses of cells before injury occurs. There is substantial evidence that iron overload in experimental animals can result in oxidative damage to lipids in vivo, once the concentration of iron exceeds a threshold level. In the liver, this lipid peroxidation is associated with impairment of membrane-dependent functions of mitochondria and lysosomes. Iron overload impairs hepatic mitochondrial respiration primarily through a decrease in cytochrome C oxidase activity, and hepatocellular calcium homeostasis may be compromised through damage to mitochondrial and microsomal calcium sequestration. DNA has also been reported to be a target of iron-induced damage, and this may have consequences in regard to malignant transformation. Mitochondrial respiratory enzymes and plasma membrane enzymes such as sodium-potassium-adenosine triphosphatase (Na(+) + K(+)-ATPase) may be key targets of damage by non-transferrin-bound iron in cardiac myocytes. Levels of some antioxidants are decreased during iron overload, a finding suggestive of ongoing oxidative stress. Reduced cellular levels of ATP, lysosomal fragility, impaired cellular calcium homeostasis, and damage to DNA all may contribute to cellular injury in iron overload. Evidence is accumulating that free-radical production is increased in patients with iron overload. Iron-loaded patients have elevated plasma levels of thiobarbituric acid reactants and increased hepatic levels of aldehyde-protein adducts, indicating lipid peroxidation. Hepatic DNA of iron-loaded patients shows evidence of damage, including mutations of the tumor suppressor gene p53. Although phlebotomy therapy is effective in removing excess iron in hereditary hemochromatosis, chelation therapy is required in the treatment of many patients who have combined secondary and transfusional iron overload due to disorders in erythropoiesis. In patients with beta-thalassemia who undergo regular transfusions, deferoxamine treatment has been shown to be effective in preventing iron-induced tissue injury and in prolonging life expectancy. The use of the oral chelator deferiprone remains controversial, and work is continuing on the development of new orally effective iron chelators.
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PMID:Iron toxicity and chelation therapy. 1241 32