Molecular aspects of the calbindins.
Studies from our laboratory concerning regulation of calbindin include regulation by 1,25-dihydroxycholecalciferol [1,25(OH)2D3], receptor regulation as a possible mechanism for modulating calbindin's response to hormone, tissue specific regulation and regulation by factors other than 1,25(OH)2D3. With regard to receptor regulation, we found that the induction of calbindin mRNA in intestine and kidney by 1,25(OH)2D3 is not accompanied by a corresponding alteration in vitamin D receptor (VDR) mRNA in the vitamin D-deficient, low calcium rat. However, in the vitamin D-replete rat, administration of 1,25(OH)2D3 results in an induction of both calbindin and VDR mRNA in these tissues. These results suggest the presence of an inhibitor of 1,25(OH)2D3-mediated receptor up-regulation in the vitamin D-deficient, low calcium animal. Glucocorticoids can also regulate calbindin gene expression. Dexamethasone treatment (50 micrograms.100 g body weight-1.d-1 for 4 d) results in a 75% decrease in rat intestinal calbindin-D9k mRNA. This decrease may be related to the inhibition of intestinal calcium absorption previously observed after glucocorticoid administration. Kidney calbindin-D28k mRNA is unaffected by glucocorticoid treatment, indicating tissue specificity of the glucocorticoid response. To evaluate more precisely the means whereby 1,25(OH)2D3 and other modulators can influence calbindin gene expression, we isolated the chromosomal gene for calbindin-D28k by screening a mouse genomic library in cosmid. Ros 17/2.8 cells were transfected with recombinant plasmids in which the mouse calbindin promoter is fused to the reporter gene encoding chloramphenicol acetyltransferase. Deletion studies have enabled us to identify sequence elements in the mouse calbindin-D28k gene that confer basal activation and a hormone inducible response.
Christakos
S
S
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714.
Gill
R
R
Lee
S
S
Li
H
H
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002117:Calcitriol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D064030:S100 Calcium Binding Protein G / Q000235:genetics*
C576499:Calb1 protein, mouse; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D005938:Glucocorticoids; D064030:S100 Calcium Binding Protein G; C576507:S100g protein, mouse; C576508:S100g protein, rat; D002117:Calcitriol