Abstract

A research program is proposed which examines several aspects of the transport, distribution and metabolism of vitamin D and its metabolities. This proposal seeks to acquire specific and detailed information about the delivery and metabolism of antiricket sterols, and to apply these findings, where possible, to the study of human physiology and disease. Two major areas of research are proposed. Project one aims to examine, by means of new or existing specific assays for vitamin D metabolites, the physiologic and pathologic influences which control vitamin D metabolism in man. Serial examination of vitamin D metabolite concentrations in human serum is designed to further our diagnostic and therapeutic capabilities in clinical disorders of mineral homeostasis. Project two deals with the serum and tissue binding proteins for antiricketic sterols, and aims to examine the specific nature of sterol transfer into tissues. Studies are designed to isolate binding proteins, examine the regulation of their synthesis, explore the possibility of specific interactions between serum binding proteins and cell surface and intracellular proteins, and examine the interaction of sterol-binding complexes with intra-cellular organelles.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM028292-05
Application #
3151868
Study Section
(SSS)
Project Start
1980-08-01
Project End
1988-03-31
Budget Start
1985-09-01
Budget End
1986-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Kelepouris, N; Harper, K D; Gannon, F et al. (1995) Severe osteoporosis in men. Ann Intern Med 123:452-60
Hu, Z Y; Blazar, P E; Haddad, J G (1995) Preventing actin interference in immunonephelometric measurements of vitamin D-binding protein (Gc-globulin). Clin Chem 41:623-5
Haddad, J G (1995) Plasma vitamin D-binding protein (Gc-globulin): multiple tasks. J Steroid Biochem Mol Biol 53:579-82
Haddad, J G; Matsuoka, L Y; Hollis, B W et al. (1993) Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest 91:2552-5
Haddad, J G; Hu, Y Z; Kowalski, M A et al. (1992) Identification of the sterol- and actin-binding domains of plasma vitamin D binding protein (Gc-globulin). Biochemistry 31:7174-81
Sanger, J M; Dabiri, G; Mittal, B et al. (1990) Disruption of microfilament organization in living nonmuscle cells by microinjection of plasma vitamin D-binding protein or DNase I. Proc Natl Acad Sci U S A 87:5474-8
Guoth, M; Murgia, A; Smith, R M et al. (1990) Cell surface vitamin D-binding protein (GC-globulin) is acquired from plasma. Endocrinology 127:2313-21
Haddad, J G; Harper, K D; Guoth, M et al. (1990) Angiopathic consequences of saturating the plasma scavenger system for actin. Proc Natl Acad Sci U S A 87:1381-5
Mc Leod, J F; Kowalski, M A; Haddad Jr, J G (1989) Interactions among serum vitamin D binding protein, monomeric actin, profilin, and profilactin. J Biol Chem 264:1260-7
Harper, K D; Iozzo, R V; Haddad, J G (1989) Receptors for and bioresponses to 1,25-dihydroxyvitamin D in a human colon carcinoma cell line (HT-29). Metabolism 38:1062-9

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