Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood erythroid progenitors (BFU-E) from patients with sickle and thalassemic syndromes were compared with those from normal individuals. The day of maximal colony formation in methyl cellulose was slightly later in the cultures from the patients with hemoglobinopathies than in the normal cultures. The number of colonies/100,000 mononuclear cells was similar in all cultures on day 13, but was higher in the hemoglobinopathy cultures on the day of maximal growth. The number of BFU-E/mL of blood was significantly higher than normal at all times in both sickle cell anemia and thalassemia. The proportional synthesis of gamma globin was twice normal in all sickle cultures, and 4 times normal in those from beta+-thalassemia. Hemin and interleukin-3 increased the numbers of erythroid colonies in all cultures, but did not consistently alter the globin synthesis patterns. Each progenitor population has a unique pattern in terms of time course, number of BFU-E, and level of gamma globin synthesis. These features indicate distinct types of BFU-E, or differences in accessory cells, or both, which distinguish blood-borne erythropoiesis in normals and those with hemoglobinopathies.
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PMID:Sickle and thalassemic erythroid progenitor cells are different from normal. 148 17

Hemin binds to isolated low-density lipoprotein (LDL) and thereby triggers LDL oxidation. In this study we investigated whether hemin can get together with LDL under physiological conditions. The relative affinity of three blood components to free hemin was as follows: RBCM < LDL < albumin. At physiological molar ratio of LDL/albumin all the hemin was bound to albumin. In molar excess of albumin over hemin, existing even under pathological conditions, albumin served as an efficient antioxidant for the plasma hemin-induced LDL oxidation. RBCM-embedded hemin, unlike plasma hemin, affected LDL: the mobile hemin was transferred from RBCM to LDL in the absence of albumin, whereas in the presence of albumin most of the mobile hemin finally reached the albumin but partially via LDL. Thus, a transient hemin is built up in LDL. This transient hemin triggered LDL oxidation which was not inhibited but rather promoted by albumin. The involvement of albumin in this oxidation was explained by its acting as a pump thereby increasing the transient hemin in LDL. It is suggested that increased membrane hemin level as in hemoglobinopathies and/or excess LDL in dyslipidemia provide conditions for hemin-induced LDL oxidation.
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PMID:The involvement of low-density lipoprotein in hemin transport potentiates peroxidative damage. 754 35

The interaction between hemin and lipid bilayers was examined from the point of view of: (a) changes in membrane permeability, (b) changes in lipid organization, (c) catalysis of lipid peroxidation. The leakage of solutes trapped in inner aqueous compartments of vesicles and liposomes increased in a concentration-dependent manner, in the range of 100-1000 microM, saturating at ca. 400 microM hemin. Under saturating conditions, leakage was essentially complete after ca. 0.5 h. Antioxidants had practically no effect upon this behavior. Extensive leakage at 5 and 10 microM hemin was observed only in the absence of antioxidants and after ca. 10 h. Electron spin resonance spectra of a spin label incorporated in oriented lipid multibilayers indicated that hemin decreased the degree of order of the bilayer. The effect was instantaneous, time-independent, and unaffected by antioxidants, displaying a concentration dependence similar to that of the permeability studies. In contrast, hemin-catalyzed lipid peroxidation displayed a bell-shaped dependence on hemin concentration, the effect ceasing at concentrations lower than those required for instantaneous permeability and structural changes. The bell-shaped behavior was found both for the detection of thiobarbituric acid-reactive compounds (TBARS) and for oxygen consumption. The time scale of TBARS formation was much slower than that for permeability changes, significant amounts of products being detected only after leakage was essentially complete. Both permeability and lipid peroxidation occurred to a larger extent in cholesterol-containing membranes. Hemin is highly aggregated in aqueous phase. Upon binding to the membrane, the aggregates undergo dissociation in a hemin/lipid ratio-dependent manner. At low ratios, hemin is largely monomeric, while at high ratios, aggregates prevail. Monomers are more effective in promoting oxidation. Aggregates are responsible for the enhancement of permeability and membrane disorder. Oxidation of membrane components is often proposed to be involved in the mechanism of hemin-promoted cell lysis. Nevertheless, the role of oxidative processes is not clear in some hemoglobinopathies. The present results provide a molecular model for an alternative mechanism of lysis that would dominate in cases where the concentration is high enough for hemin to aggregate.
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PMID:Hemin-induced lipid membrane disorder and increased permeability: a molecular model for the mechanism of cell lysis. 823 71