Abstract

The proposed research is aimed at (1) further definition of the molecular mechanisms of deoxy-Hb S polymerization and gelation, by mapping of intermolecular contact sites for each tetramer subunit, studies of the role of non S Hbs in polymerization, and the effect of Hb dissociation equilibria and hybrid formation in polymerization in red cells, and interactions of Hbs S and C; (2) further studies of functional properties of HbS-containing-red cells, (3) examination of the functional abnormalities (and their structural basis) of rbc membranes in SS, CC and other abnormal red cells. These studies are designed to further our knowledge of the mechanisms of sickling, to aid in the design and application of antisickling agents, to determine physiological conditions dangerous or favorable to persons with various sickling disorders, and to explore the pathophysiology of the red cell membranes with the overall aim of improving cell survival and function in these disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028018-18
Application #
3339441
Study Section
(EH)
Project Start
1981-07-01
Project End
1986-09-29
Budget Start
1985-07-01
Budget End
1986-09-29
Support Year
18
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Tiffert, Teresa; Daw, Nuala; Etzion, Zipora et al. (2007) Age decline in the activity of the Ca2+-sensitive K+ channel of human red blood cells. J Gen Physiol 129:429-36
Lew, Virgilio L; Daw, Nuala; Etzion, Zipora et al. (2007) Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells. Blood 110:1334-42
Amer, Johnny; Etzion, Zipora; Bookchin, Robert M et al. (2006) Oxidative status of valinomycin-resistant normal, beta-thalassemia and sickle red blood cells. Biochim Biophys Acta 1760:793-9
Lew, Virgilio L; Tiffert, Teresa; Etzion, Zipora et al. (2005) Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells. Blood 105:361-7
Lew, Virgilio L; Daw, Nuala; Perdomo, Deisy et al. (2003) Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells. Blood 102:4206-13
Lew, Virgilio L; Etzion, Zipora; Bookchin, Robert M (2002) Dehydration response of sickle cells to sickling-induced Ca(++) permeabilization. Blood 99:2578-85
de Jong, K; Larkin, S K; Styles, L A et al. (2001) Characterization of the phosphatidylserine-exposing subpopulation of sickle cells. Blood 98:860-7
Raftos, J E; Edgley, A; Bookchin, R M et al. (2001) Normal Ca2+ extrusion by the Ca2+ pump of intact red blood cells exposed to high glucose concentrations. Am J Physiol Cell Physiol 280:C1449-54
Bookchin, R M; Etzion, Z; Sorette, M et al. (2000) Identification and characterization of a newly recognized population of high-Na+, low-K+, low-density sickle and normal red cells. Proc Natl Acad Sci U S A 97:8045-50
Bookchin, R M; Balazs, T; Wang, Z et al. (1999) Polymer structure and solubility of deoxyhemoglobin S in the presence of high concentrations of volume-excluding 70-kDa dextran. Effects of non-s hemoglobins and inhibitors. J Biol Chem 274:6689-97

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