The objective is to determine the contributions of reduced cellular deformability and cell surface changes to increased red cell destruction in various human hemolytic disorders and to define the biochemical and structural basis of the deformability and cell surface changes. Studies are designed with the following specific aims: 1) establish that maintenance of redundant surface area is essential for normal red cell life span; 2) determine if increases in cytoplasmic viscosity or in membrane rigidity, in and of themselves, decrease red cell life span; 3) establish that interaction of hemoglobin and excess unmatched globin chains with red cell membrane results in marked alterations of cellular properties; 4) define the contribution of increased pathologic red cell interaction with monocytes and macrophages to decreased red cell life span in various hemolytic anemias; 5) define the functional role of membrane skeletal proteins, glycoproteins, and other antigenic determinants in regulating cellular properties; and 6) establish the importance of glycolytic enzymes in maintaining the structural integrity of the membrane and the cell. Ektacytometry of cell suspensions and micromechanical experiments on individual red cells will be used to quantitate the deformability of red cells. A newly developed micromechanical method to study the interaction of individual red cells with monocytes will be used to document cell surface changes. Measurements will be performed on density fractionated cell populations in order to document the heterogeneity of various cellular changes. Detailed characterization of cell deformability and cell surface changes in various hemolytic anemias, and relating the measured changes to severity of the anemia, may enable us to define the important cellular determinants of red cell life span. Our emphasis on obtaining basic biological and biophysical information using novel techniques may also provide new insights into the structural organization of the red cell membrane. Successful completion of the proposed studies should contribute to a better understanding of the pathophysiology of various human hemolytic anemias.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026263-12
Application #
3227803
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1980-07-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
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Pimentel, Harold; Parra, Marilyn; Gee, Sherry L et al. (2016) A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis. Nucleic Acids Res 44:838-51

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