| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 17, 2004
Accepted on July 14, 2004
,25(OH)2-vitamin D3 in vivo and in vitro
Department of Biochemistry, University of California, Riverside CA 92521, USA
* To whom correspondence should be addressed. E-mail: anthony.norman{at}ucr.edu.
The steroid hormone 1
,25(OH)2-vitamin D3 (1,25D) regulates gene transcription through a nuclear receptor (VDR) and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). This study characterized the VDRmem present in a caveolae-enriched membrane fraction (CMF), a site of accumulation of signal transduction agents. Saturable and specific [3H]-1,25D binding in vitro was found in CMF of chick, rat and mouse intestine, mouse lung and kidney, and human NB4 leukemia and rat ROS 17/2.8 osteoblast-like cells; in all cases the 1,25D KD = 1-3 nM. Our data collectively support the classical VDR being the VDRmem in caveolae: (a) VDR antibody immunoreactivity was detected in CMF of all tissues tested; (b) competitive binding of [3H]-1,25D by eight analogs of 1,25D was significantly correlated between nuclei and CMF (r2=0.95) but not between vitamin D binding protein (has a different ligand binding specificity) and CMF; (c) confocal immunofluorescence microscopy of ROS 17/2.8 cells showed VDR in close association with with the caveolae marker protein, caveolin-1, in the plasma membrane region; (d) in vivo 1,25D pretreatment reduced in vitro [3H]-1,25D binding by 30% in chick and rat intestinal CMF demonstrating in vivo occupancy of the CMF receptor by 1,25D; and (e) comparison of [3H]-1,25D binding in VDR KO and WT mouse kidney tissue showed 85% reduction in VDR KO CMF and 95% reduction in VDR KO nuclear fraction. This study supports the presence of VDR as the 1,25D-binding protein associated with plasma membrane caveolae.
,25(OH)2-vitamin D3 •
VDR •
VDR knock-out •
membrane receptor
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  A. W Norman From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health Am. J. Clinical Nutrition, August 1, 2008; 88(2): 491S - 499S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. X. Tishkoff, K. A. Nibbelink, K. H. Holmberg, L. Dandu, and R. U. Simpson Functional Vitamin D Receptor (VDR) in the T-Tubules of Cardiac Myocytes: VDR Knockout Cardiomyocyte Contractility Endocrinology, February 1, 2008; 149(2): 558 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Hammes and E. R. Levin Extranuclear Steroid Receptors: Nature and Actions Endocr. Rev., December 1, 2007; 28(7): 726 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Norman Vitamin D Receptor: New Assignments for an Already Busy Receptor Endocrinology, December 1, 2006; 147(12): 5542 - 5548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ma, W.-D. Yu, R.-X. Kong, D. L. Trump, and C. S. Johnson Role of Nongenomic Activation of Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase/Extracellular Signal-Regulated Kinase 1/2 Pathways in 1,25D3-Mediated Apoptosis in Squamous Cell Carcinoma Cells Cancer Res., August 15, 2006; 66(16): 8131 - 8138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Moosgaard, P Vestergaard, L Heickendorff, F Melsen, P Christiansen, and L Mosekilde Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study. Eur. J. Endocrinol., August 1, 2006; 155(2): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Meier, O. Gressner, F. Lammert, and A. M. Gressner Gc-Globulin: Roles in Response to Injury Clin. Chem., July 1, 2006; 52(7): 1247 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Bula, J. Huhtakangas, C. Olivera, J. E. Bishop, A. W. Norman, and H. L. Henry Presence of a Truncated Form of the Vitamin D Receptor (VDR) in a Strain of VDR-Knockout Mice Endocrinology, December 1, 2005; 146(12): 5581 - 5586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. McVoy and R. R. Kew CD44 and Annexin A2 Mediate the C5a Chemotactic Cofactor Function of the Vitamin D Binding Protein J. Immunol., October 1, 2005; 175(7): 4754 - 4760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Dusso, A. J. Brown, and E. Slatopolsky Vitamin D Am J Physiol Renal Physiol, July 1, 2005; 289(1): F8 - F28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ochiai, D. Miura, H. Eguchi, S. Ohara, K. Takenouchi, Y. Azuma, T. Kamimura, A. W. Norman, and S. Ishizuka Molecular Mechanism of the Vitamin D Antagonistic Actions of (23S)-25-Dehydro-1{alpha}-Hydroxyvitamin D3-26,23-Lactone Depends on the Primary Structure of the Carboxyl-Terminal Region of the Vitamin D Receptor Mol. Endocrinol., May 1, 2005; 19(5): 1147 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Vertino, C. M. Bula, J.-R. Chen, M. Almeida, L. Han, T. Bellido, S. Kousteni, A. W. Norman, and S. C. Manolagas Nongenotropic, Anti-Apoptotic Signaling of 1{alpha},25(OH)2-Vitamin D3 and Analogs through the Ligand Binding Domain of the Vitamin D Receptor in Osteoblasts and Osteocytes: MEDIATION BY Src, PHOSPHATIDYLINOSITOL 3-, AND JNK KINASES J. Biol. Chem., April 8, 2005; 280(14): 14130 - 14137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Adachi, Y. Honma, H. Masuno, K. Kawana, I. Shimomura, S. Yamada, and M. Makishima Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative J. Lipid Res., January 1, 2005; 46(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
