Vitamin D receptor is not required for the rapid actions of 1,25-dihydroxyvitamin D3 to increase intracellular calcium and activate protein kinase C in mouse osteoblasts

The rapid, non‐genomic actions of 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] have been well described, however, the role of the nuclear vitamin D receptor (VDR) in this pathway remains unclear. To address this question, we used VDR(+/+) and VDR(−/−) osteoblasts isolated from wild‐type and VDR null mice...

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Published in:Journal of cellular biochemistry Vol. 88; no. 4; pp. 794 - 801
Main Authors: Wali, Ramesh K., Kong, Juan, Sitrin, Michael D., Bissonnette, Marc, Li, Yan Chun
Format: Journal Article
Language:English
Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.03.2003
Subjects:
Animals
Calcitriol - pharmacology
Calcitriol - physiology
calcium
Calcium - analysis
Calcium - metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Indoles - pharmacology
Isoenzymes - biosynthesis
Maleimides - pharmacology
Mice
Mice, Knockout
non-genomic actions
Osteoblasts - drug effects
Osteoblasts - physiology
Phosphorylation - drug effects
protein kinase C
Protein Kinase C - analysis
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - biosynthesis
Protein Kinase C - metabolism
Receptors, Calcitriol - genetics
Receptors, Calcitriol - physiology
RNA - analysis
RNA - isolation & purification
VDR
vitamin D
ISSN:0730-2312, 1097-4644
Online Access:Get full text
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Summary:The rapid, non‐genomic actions of 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] have been well described, however, the role of the nuclear vitamin D receptor (VDR) in this pathway remains unclear. To address this question, we used VDR(+/+) and VDR(−/−) osteoblasts isolated from wild‐type and VDR null mice to study the increase in intracellular calcium ([Ca2+]i) and activation of protein kinase C (PKC) induced by 1,25(OH)2D3. Within 1 min of 1,25(OH)2D3 (100 nM) treatment, an increase of 58 and 53 nM in [Ca2+]i (n = 3) was detected in VDR(+/+) and VDR(−/−) cells, respectively. By 5 min, 1,25(OH)2D3 caused a 2.1‐ and 1.9‐fold increase (n = 6) in the phosphorylation of PKC substrate peptide acetylated‐MBP4–14 in VDR(+/+) and VDR(−/−) osteoblasts. The 1,25(OH)2D3‐induced phosphorylation was abolished by GF109203X, a general PKC inhibitor, in both cell types, confirming that the secosteroid induced PKC activity. Moreover, 1,25(OH)2D3 treatment resulted in the same degree of translocation of PKC‐α and PKC‐δ, but not of PKC‐ζ, from cytosol to plasma membrane in both VDR(+/+) and VDR(−/−) cells. These experiments demonstrate that the 1,25(OH)2D3‐induced rapid increases in [Ca2+]i and PKC activity are neither mediated by, nor dependent upon, a functional nuclear VDR in mouse osteoblasts. Thus, VDR is not essential for these rapid actions of 1,25(OH)2D3 in osteoblasts. © 2003 Wiley‐Liss, Inc.
Bibliography:NIH - No. DK59327
istex:CD30B7BA8F165602FDA8833958CB8D1A2051279F
ark:/67375/WNG-VND4G284-4
ArticleID:JCB10432
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.10432