CA++ BINDING PROTEINS AND THE VITAMIN D ENDOCRINE SYSTEM

Project Details

Description

Previous investigations have demonstrated that besides the
intestine at least 20 tissues including kidney, pancreas, skin and
brain all have receptors for 1,25dihydroxyvitamin D3
(1,25(OH)2D3) and/or a vitamin D induced calcium binding protein
(CaBP), thus suggesting a wider role for vitamin D in calcium
metabolism than merely intestinal calcium absorption. The object
of this proposal is to obtain a better understanding of the multiple
actions of the vitamin D endocrine system by studying the
function and regulation of the mammalian 28,000 Mr vitamin D
dependent CaBP. Two working hypotheses will be tested: (1) that
CaBP may have an important fundamental role in mediating
intracellular calcium dependent processes and (2) that factors
other than or in addition to 1,25(OH)2D3 may modulate CaBP
mRNA and the subsequent synthesis of the protein. In an effort
to establish the functional significance of CaBP, provocative
preliminary results concerning a dose-dependent inhibition by
CaBP of Ca++ dependent protein kinase will be pursued. In order
to examine the possibility that CaBP may participate in synaptic
events, we will extend our preliminary findings concerning the
presence of CaBP in synaptosomes and we will test the ability of
CaBP to activate Ca-Mg ATPase. We will use the gel overlay
technique in order to determine whether specific binding proteins
for CaBP can be detected and identified. In addition, using the
DNA probe complementary to CaBP mRNA and recombinant DNA
techniques, we will study the regulation of mammalian CaBP both
in vivo and in vitro. Changes in CaBP gene expression during
development will be examined and studies concerning the
regulation of human CaBP will be initiated. The nucleotide
sequence of CaBP will be determined and studies concerning the
regulation of CaBP gene expression using transfected cells will be
initiated. It is likely that important advances to the
understanding of vitamin D regulated calcium homeostasis can be
made by examining molecular level changes. Implicit in this study
is facilitation of a more detailed understanding of how
1,25(OH)2D3 is involved in the many disease processes involved
with abnormalities in the calcium homeostatic process such as
osteomalacia, osteoporosis and perturbations of parathyroid
function. Additionally, this study may lead to an increased
understanding of the role of the vitamin D endocrine system in
normal brain function as well as in brain disorder involving
calcium dependent functions.
StatusFinished
Effective start/end date9/10/876/30/13

Funding

  • National Institutes of Health: $264,352.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $300,306.00
  • National Institutes of Health: $303,340.00
  • National Institutes of Health: $50,134.00
  • National Institutes of Health: $302,398.00
  • National Institutes of Health: $146,299.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $15,600.00
  • National Institutes of Health: $318,775.00
  • National Institutes of Health: $264,352.00
  • National Institutes of Health: $222,334.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $161,614.00
  • National Institutes of Health: $309,531.00
  • National Institutes of Health: $264,352.00
  • National Institutes of Health: $216,122.00
  • National Institutes of Health
  • National Institutes of Health: $209,773.00
  • National Institutes of Health
  • National Institutes of Health: $354,191.00

ASJC

  • Medicine(all)

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