Induction of Calbindin

1 Induction of Calbindin-D In response to calcitriol administration, there is an increase in mRNA synthesis and then in the synthesis of calbindin-D in intestinal mucosal cells, which is correlated with the later and more sustained increase in calcium absorption. In vitamin D-deficient animals, there is no detectable calbindin in the intestinal mucosa, whereas in animals adequately provided with vitamin D, it may account for 1 % to 3% of soluble protein in the cytosol of the colunmar epithelial ceils. Although the rapid response to calcitriol is an increase in the permeability of the brush border membrane to calcium, the induction of calbindin permits intracellular accumulation and transport of calcium. The rapid increase in net calcium transport in tissue from vitamin D-replete animals is presumably dependent on the calbindin that is already present in deficient animals, there can be no increase in calcium transport until sufficient calbindin has accumulated to permit intracellular accumulation, despite the increased permeability of the brush border. 

Calbindin is a relatively small protein (the chick protein has an Mr of28,000, whereas those from mammalian intestinal mucosa have Mr between 8,000 to 11,000) and binds calcium with high affinity (kfdiss 1 — 10 x 10 M). The mammalian intestinal protein (calbindin-D9k) has two calcium binding 

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Early experiments demonstrated that actinomycin D and alpha-amanitin could block induction of calbindin-D28K by l,25(OH)2D3 [9]. It was later demonstrated that l,25(OH)2D3 was able to stimulate general RNA synthesis in the chick intestine [11] as well as specifically inducing calbindin-D28K mRNA [12]. In addition,... 

With the isolated perfused duodenum, there is a rapid increase in calcium transport in response to the addition of calcitriol to the perfusion medium. Isolated enterocytes and osteoblasts also show a rapid increase in calcium uptake in response to calcitriol. It is not associated with changes in mRNA or protein synthesis, but seems to be because of recruitment of membrane calcium transport proteins from intracellular vesicles to the cell surface. It is inhibited by the antimicrotubule compound colchicine. It can only be demonstrated in tissues from animals that are adequately supplied with vitamin D in vitamin D-deficient animals, the increase in intestinal calcium absorption occurs only more slowly, together with the induction of calbindin. 

Although calcitriol is synthesized only in the proximal renal tubule, after the administration of pHJcalcidiol, radioactivity in the kidney accumulates only in the distal and collecting tubules. This is the region in which selective resorption of calcium from the urine occurs and, in response to calcitriol, there is induction of calbindin-D28k. As in the intestinal mucosa, calbindin in the kidney is a cytosolic protein and is presumably involved in the intracellular accumulation and transport of calcium. 

Adipocytes have vitamin D receptors, and there is evidence that vitamin D may act as a suppressor of adipocyte development (Kawada et al., 1996). It has been suggested that vitamin D inadequacy may be a factor in the development of the metabolic syndrome ( syndrome X, the combination of insulin resistance, hyperlipidemia, and atherosclerosis associated with abdominal obesity). Sunlight exposure, and hence vitamin D status, may be a factor in the difference in incidence of atherosclerosis and myocardial infarction between northern and southern European countries in addition to effects on adipocyte development, calcitriol also enhances insulin secretion through induction of calbindin-D (Section 3.3.7.1), and there is some evidence vitamin D supplements can improve glucose tolerance (Boucher, 1998). 

Ferrari, S., Mohnari, S., Battini, R., et al. 1992. Induction of calbindin-D28k by 1,25-dihydroxyvitamin D3 in cultured chicken intestinal cells. Exp. Cell Res. 200 528-31. 

Gagnon, A., Simboli-CampbeU, M., Welsh, J. 1994. Induction of calbindin D-28k in Madin-Darby bovine kidney cells by l,25(OH)2D3. Kidney Int. 45 95-102. 

Early studies showed that, after the administration of [ H]cholecalciferol or ergocalciferol to vitamin D-deficient animals, there is marked accumulation of [ H] calcitriol in the nuclei of intestinal mucosal cells. Physiological doses of vitamin D cause an increase in the intestinal absorption of calcium in deficient animals the response is faster after the administration of calcidiol and faster stUl after calcitriol. There are two separate responses of intestinal mucosal cells to calcitriol a rapid increase in calcium uptake that is due to recruitment of calcium transporters to the cell surface (Section 3.3.2) and a later response from the induction of a calcium binding protein, calbindin-D. 

Lila, D., Susana, Z. Ricardo, B. (1994). Induction of a calbindin-Dgic-like protein in avian muscle cells by 1,25-dihydroxy-vitamin Dj. Biochem. Mol. Biol. Int, 32,859-67. 

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