Ferritin is abundant in specialized cells of iron storage, the hepatocyte and RE cells of adults and embryos and the erythrocytes of embryos (an unusually Mobile storage site). The regulation of red cell ferritin synthesis and the structure of red cell ferritin related to function was investigated. Regulation: Iron increased the use of preformed ferritin mRNA; high concentration and saturation of transferrin coincided with erythrocyte iron storage; a histone 2A subtype was correlated with inducible ferritin synthesis being present in mature embryonic cells, immature embryonic and adult cells, and absent in adult erythrocytes. Structure: An Fe2+ - Fe3+ binding site on apoferritin was demonstrated which affected iron deposition; phosphorylation of red cell ferritin-specific serine was demonstrated which increased iron release in vitro. The results are compatible with two hypothesis: (1) regulation of red cell ferritin synthesis in adults and embryos depends both on the extracellular environment (transferrin concentration and saturation) and the intracellular environment (storage of ferritin mRNA, histone 2A variants); (2) cell-specific differences in the protein shell of ferritin, altered by phosphorylation e.g., affect availability of stored iron in vivo, thereby explaining the use of the red cell as a storage site in embryos when the iron demand is high. The two hypotheses will be tested by investigating, in relation to iron storage, Regulation: (1) translational control of ferritin synthesis by iron; (2) changes in histone 2A structure; change of concentration in ferritin gene transcripts of adult and embryonic red cells and mutant and normal murine cells; (3) transferrin binding by adult and embryonic red cells; Structure: (4) red cell ferritin phosphorylation in vitro and in vivo; (5) the Fe-apoferritin binding site in modified ferritin, during oxidation of Fe2+, influenced by Pi. The results will be important for understanding general mechanisms of cell development, translational control of protein synthesis and iron protein interactions and specific knowledge of normal and abnormal (e.g. thalassemic) erythropoiesis and iron metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM020251-09
Application #
3151291
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1977-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Type
Earth Sciences/Resources
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695