Selected aspects of fatty acid metabolism, which are considered to have important roles in maturation and differention, will be studied using isolated subpopulations of guinea pig megakaryocytes that are relatively homogeneous in regard to phases of maturation. The enzymatic basis of the observation that de novo fatty acid synthesis occurs primarily in mature megakaryocytes and not in immature megakaryocytes will be studied by both immunologic and radiometric enzyme assays. The two primary enzymes involved in fatty acid synthesis, fatty acid synthase and acetyl-CoA carboxylase, will be assessed using immunologic methods as well as enzymatic determinations on defined subpopulations of megakaryocytes. Correlations between presence of enzyme by either technique and morphologic stage, ploidy and size of cells and protein content will be made. As acylation reactions appear to be altered during megakaryocyte maturation, acetyl transferase activities and CoA-independent and CoA-dependent transacylase activities will be determined on isolated fractions of megakaryocytes. The activity of delta-5 and 6 desaturases, key enzymes in the de novo synthesis of arachidonic acid, will be investigated in megakaryocytes at various stages of maturation to determine whether de novo synthesis of arachidonic acid is more active at specific stages of megakaryocyte maturation. The results of these studies should further define the relationship between fatty acid metabolism and megakaryocyte maturation and provide new information in regard to membrane biogenesis in megakaryocytes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL025455-12
Application #
3338084
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1988-07-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Schick, P K; Walker, J; Profeta, B et al. (1997) Synthesis and secretion of von Willebrand factor and fibronectin in megakaryocytes at different phases of maturation. Arterioscler Thromb Vasc Biol 17:797-801
Schick, P K; Wojenski, C M; Bennett, V D et al. (1996) The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes. Blood 87:1817-23
Schick, P K; Wojensk, C M; Bennett, V et al. (1996) Fibronectin isoforms in megakaryocytes. Stem Cells 14 Suppl 1:212-9
Schick, P K; Walker, J (1996) The acylation of megakaryocyte proteins: glycoprotein IX is primarily myristoylated while glycoprotein Ib is palmitoylated. Blood 87:1377-84
He, X; Schick, P K; Wojenski, C (1995) The expression of acetyl coenzyme A carboxylase is related to megakaryocyte maturation. J Lab Clin Med 126:178-83
Konkle, B A; Schick, P K; He, X et al. (1993) Plasminogen activator inhibitor-1 mRNA is expressed in platelets and megakaryocytes and the megakaryoblastic cell line CHRF-288. Arterioscler Thromb 13:669-74
Schick, P K; Wojenski, C M; Walker, J (1993) The effects of olive oil, hydrogenated palm oil, and omega-3 fatty acid-enriched diets on megakaryocytes and platelets. Arterioscler Thromb 13:84-9
Wojenski, C M; Schick, P K (1993) Development of storage granules during megakaryocyte maturation: accumulation of adenine nucleotides and the capacity for serotonin sequestration. J Lab Clin Med 121:479-85
Schick, P K; Konkle, B A; He, X et al. (1993) P-selectin mRNA is expressed at a later phase of megakaryocyte maturation than mRNAs for von Willebrand factor and glycoprotein Ib-alpha. J Lab Clin Med 121:714-21
Schick, P K; Williams-Gartner, K; He, X L (1990) Lipid composition and metabolism in megakaryocytes at different stages of maturation. J Lipid Res 31:27-35

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