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 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) and/or a vitamin D
induced calcium binding protein (CaBP); thus suggesting a wider role for
the vitamin D endocrine system in calcium metabolism than mere 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 biochemistry, function and regulation of the mammalian vitamin
D-dependent calcium binding proteins and by testing the hypothesis that
proteins other than CaBP are induced by 1,25(OH)2D3. The mammalian vitamin
D-dependent calcium binding proteins will be biochemically characterized
and compared to other calcium binding proteins. Also, in order to
determine whether the mammalian vitamin D-dependent CaBPs have enzyme
modulating abilities, similar to calmodulin, we will test the ability of
these proteins to activate Ca/Mg ATPase, alkaline phosphatase and
phosphodiesterase. Binding to phenothiazine and cross-reactivity in the
calmodulin redioimmunoassay will also be investigated. We will test how
dietary alterations affect renal CaBP as well as how vitamin D deficiency
and vitamin D administration affect both renal CaBP as well as how vitamin
D deficiency and vitamin D administration affect both renal and brain
CaBP. We also propose to study, using a reticulocyte lysate cell free
system, the molecular mechanisms involved in the induction of CaBP in
mammalian kidney and brain. 2-D gel electrophoretic patterns of mRNA
translation products will be used to examine the specificity of the
response at the mRNA level in the kidney and brain. Studies to determine
whether proteins other than calcium binding protein are induced in rat
kidney are also proposed. This study, by extending provocative preliminary
findings, will increase our understanding of the vitamin D endocrine system
and therefore of the many disease processes associated with abnormalities
in the calcium homeostatic process such as osteomalacia, osteoporosis, and
pertubations 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 disorders involving calcium
dependent functions.
StatusFinished
Effective start/end date7/1/836/30/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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