Although sickle cell disease is a disease related to abnormal hemoglobin iside the red cell, a variety of morphologcal and functional abnormalities have been identified in the membranes of sickle cells called irreversibly sickled cells (ISC). These ISC are highly dehydrated and have reduced deformability, altered membrane phospholipid organization, hypercoagulability, and increased tendency to adhere to vascular endothelium. These abnormalities of ISC as well as a relationship between ISC counts and reduced red cell survival, conjunctival blood vessel abnormalities, and occurrence of leg ulcers suggest a potential role for ISC in the pathogenesis of sickle cell disease.
The aim of this project is to discover whether there is any correlation between the degree of membrane lipid peroxidaition, altered lipid asymmetry and hypercoagulability in varying density fractions of sickle cells separated on Stractan density gradients and whether these membrane abnormalities are present only in the ISC due to sickling or are abnormalities that accrue gradually to membrane damage. In vitro cellular dehydration induced by Nystatin treatment to discoid sickle cells will be used to discriminate predominant role of membrane damage versus cellular dehydration per se in the hypercoagulability, altered membrane lipid asymmetry and peroxidative membrane lipid damage of sickle cells. This project also will explore whether exogenous peroxidant threat in vitro to discoid sickle cells can generate ISC comparable to in vivo-formed ISC fractionated from sickle blood. Standard techniques for analyses of membrane lipid peroxidation, membrane phospholipid organization, coagulability, and proteins will be utilized and have been standardized in this laboratory. Data from at least 20 sickle cell patients will be analyzed statistically.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030247-02
Application #
3341312
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Type
Schools of Medicine
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103
Jain, S K; Ross, J D; Levy, G J et al. (1990) The effect of malonyldialdehyde on viscosity of normal and sickle red blood cells. Biochem Med Metab Biol 44:37-41
Jain, S K; Ross, J D; Duett, J et al. (1990) Low plasma prealbumin and carotenoid levels in sickle cell disease patients. Am J Med Sci 299:13-5
Jain, S K; Levine, S N; Duett, J et al. (1990) Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39:971-5
Jain, S K (1989) The neonatal erythrocyte and its oxidative susceptibility. Semin Hematol 26:286-300
Jain, S K; Ross, J D; Levy, G J et al. (1989) The accumulation of malonyldialdehyde, an end product of membrane lipid peroxidation, can cause potassium leak in normal and sickle red blood cells. Biochem Med Metab Biol 42:60-5
Jain, S K; McVie, R; Duett, J et al. (1989) Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes 38:1539-43
Jain, S K (1989) Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem 264:21340-5
Jain, S K; Williams, D M (1988) Copper deficiency anemia: altered red blood cell lipids and viscosity in rats. Am J Clin Nutr 48:637-40
Jain, S K (1988) Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes. Biochim Biophys Acta 937:205-10
Jain, S K (1987) Elevated malonyldialdehyde levels, altered membrane lipid asymmetry, and hypercoagulability of erythrocytes from newborn infants. Biomed Biochim Acta 46:S21-5

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