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991.
Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein 总被引:6,自引:0,他引:6
Gell D Kong Y Eaton SA Weiss MJ Mackay JP 《The Journal of biological chemistry》2002,277(43):40602-40609
Alpha-hemoglobin stabilizing protein (AHSP) is a small (12 kDa) and abundant erythroid-specific protein that binds specifically to free alpha-(hemo)globin and prevents its precipitation. When present in excess over beta-globin, its normal binding partner, alpha-globin can have severe cytotoxic effects that contribute to important human diseases such as beta-thalassemia. Because AHSP might act as a chaperone to prevent the harmful aggregation of alpha-globin during normal erythroid cell development and in diseases of globin chain imbalance, it is important to characterize the biochemical properties of the AHSP.alpha-globin complex. Here we provide the first structural information about AHSP and its interaction with alpha-globin. We find that AHSP is a predominantly alpha-helical globular protein with a somewhat asymmetric shape. AHSP and alpha-globin are both monomeric in solution as determined by analytical ultracentrifugation and bind each other to form a complex with 1:1 subunit stoichiometry, as judged by gel filtration and amino acid analysis. We have used isothermal titration calorimetry to show that the interaction is of moderate affinity with an association constant of 1 x 10(7) m(-1) and is thus likely to be biologically significant given the concentration of AHSP (approximately 0.1 mm) and hemoglobin (approximately 4 mm) in the late pro-erythroblast. 相似文献
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994.
Studies using infrared, (1)H and (13)C nuclear magnetic resonance, and X-ray photoelectron spectroscopies and differential scanning calorimetry support the hypothesis that hydrogen bonds, formed between the carboxylic acid functionality of the mucoadhesive material poly(acrylic acid) and the glycoprotein component of mucus, play a significant role in the process of mucoadhesion. There are fewer H-bonded interactions between the components than within the bulk of the pure mucoadhesive agent. The pH of the medium influences the structures of both the poly(acrylic acid) and the mucus, which, in turn, determine the nature and the extent of mucoadhesive interactions. 相似文献
995.
To understand the physical basis of the wide variety of shapes of deoxygenated red cells from patients with sickle cell anemia, we have measured the formation rate and volume distribution of the birefringent domains of hemoglobin S fibers. We find that the domain formation rate depends on the approximately 80th power of the protein concentration, compared to approximately 40th power for the concentration dependence of the reciprocal of the delay time that precedes fiber formation. These remarkably high concentration dependences, as well as the exponential distribution of domain volumes, can be explained by the previously proposed double nucleation model in which homogeneous nucleation of a single fiber triggers the formation of an entire domain via heterogeneous nucleation and growth. The enormous sensitivity of the domain formation rate to intracellular hemoglobin S concentration explains the variable cell morphology and why rapid polymerization results in cells that do not appear sickled at all. 相似文献
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997.
Exposure of mammals to hyperoxia causes pulmonary and ocular pathology. Hyperoxic damage and cell death may derive from enhanced intracellular formation of reactive oxygen species (ROS), probably of mitochondrial origin. There is, however, controversy on this point. When wild-type and respiration-deficient (rho(o)) HeLa cells were cultured in 80% O2, wild-type cells stopped growing after 5 days and died thereafter whereas rho(o) cells survived and grew to confluence. This tolerance of rho(o) cells for hyperoxia was not associated with greater resistance to oxidants such as hydrogen peroxide and t-butyl hydroperoxide. Under both 20% and 80% O2, rho(o) cells exhibited substantially decreased ROS production, and, under 80% O2, rho(o) cells showed no suppression of aconitase activity or mitochondrial protein carbonyl formation. Replacement of normal mitochondria in rho(o) cells restored ROS production and susceptibility to hyperoxia. Two other approaches that diminished mitochondrial ROS generation also increased tolerance for hyperoxia. HeLa cells constantly exposed to the protonophoric uncoupler carbonyl cyanide m-chlorophenylhydrazone, which enhances respiration but decreases ROS production, showed preferential survival under 80% O2, as did HeLa cells treated with chloramphenicol, which suppresses both respiration and mitochondrial ROS production. We conclude that interactions between respiring mitochondria and O2 are primarily responsible for hyperoxic cell damage. 相似文献
998.
Mechanisms of Aldosterone's Action on Epithelial Na + Transport 总被引:1,自引:0,他引:1
Aldosterone maintains total organism sodium balance in all higher vertebrates. The level of sodium reabsorption is primarily determined by the action of aldosterone on epithelial sodium channels (ENaC) in the distal nephron. Recent work shows that, in an aldosterone-sensitive renal cell line (A6), aldosterone regulates sodium reabsorption by short- and long-term processes. In the short term, aldosterone regulates sodium transport by inducing expression of the small G-protein, K-Ras2A, by stimulating the activity of methyl transferase and S-adenosyl-homocysteine hydrolase to activate Ras by methylation, and, possibly, by subsequent activation by K-Ras2A of phosphatidylinositol phosphate-5-kinase (PIP-5-K) and phosphatidylinositol-3-kinase (PI-3-K), which ultimately activates ENaC. In the long term, aldosterone regulates sodium transport by altering trafficking, assembly, and degradation of ENaC. 相似文献
999.
The formation of morphogen gradients is essential for tissue patterning. Morphogens are released from producing cells and spread through adjacent tissue; paradoxically, however, many morphogens, including Wingless, associate tightly with the cell membrane. Here, we describe a novel cell biological mechanism that disperses membrane fragments over large distances through the Drosophila imaginal disc epithelium. We call these membrane exovesicles argosomes. Argosomes are derived from basolateral membranes and are produced by many different regions of the disc. They travel through adjacent tissue where they are found predominantly in endosomes. Wingless protein colocalizes with argosomes derived from Wingless-producing cells. The properties of argosomes are consistent with their being a vehicle for the spread of Wingless protein. 相似文献
1000.