|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 33, 30337-30350, August 16, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Medicine, Physiology, and Human Genetics,
McGill University and Royal Victoria Hospital, Montreal,
Quebec H3A 1A1, Canada
The calcium-sensing receptor (CASR), expressed in
parathyroid chief cells, thyroid C-cells, and cells of the kidney
tubule, is essential for maintenance of calcium homeostasis. Here we
show parathyroid, thyroid, and kidney CASR mRNA levels increased
2-fold at 15 h after intraperitoneal injection of
1,25-dihydroxyvitamin D3
(1,25(OH)2D3) in rats. Human thyroid C-cell
(TT) and kidney proximal tubule cell (HKC) CASR gene transcription
increased ~2-fold at 8 and 12 h after
1,25(OH)2D3 treatment. The human CASR gene has
two promoters yielding alternative transcripts containing either exon
1A or exon 1B 5'-untranslated region sequences that splice to exon 2 some 242 bp before the ATG translation start site. Transcriptional
start sites were identified in parathyroid gland and TT cells; that for
promoter P1 lies 27 bp downstream of a TATA box, whereas that for
promoter P2, which lacks a TATA box, lies in a GC-rich region. In HKC
cells, transcriptional activity of a P1 reporter gene construct was
11-fold and of P2 was 33-fold above basal levels. 10 The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY116081 and AY116082.
Human Calcium-sensing Receptor Gene
VITAMIN D RESPONSE ELEMENTS IN PROMOTERS P1 AND P2 CONFER
TRANSCRIPTIONAL RESPONSIVENESS TO 1,25-DIHYDROXYVITAMIN D*
and
8
M 1,25(OH)2D3 stimulated P1
activity 2-fold and P2 activity 2.5-fold. Vitamin D response elements
(VDREs), in which half-sites (6 bp) are separated by three nucleotides,
were identified in both promoters and shown to confer
1,25(OH)2D3 responsiveness to a heterologous promoter. This responsiveness was lost when the VDREs were mutated. In
electrophoretic mobility shift assays with either in vitro transcribed/translated vitamin D receptor and retinoid X receptor-
, or HKC nuclear extract, specific protein-DNA complexes were formed in
the presence of 1,25(OH)2D3 on oligonucleotides
representing the P1 and P2 VDREs. In summary, functional VDREs have
been identified in the CASR gene and provide the mechanism whereby
1,25(OH)2D up-regulates parathyroid, thyroid C-cell, and
kidney CASR expression.
*
This work was supported in part by Canadian Institutes of
Health Research (CIHR) Grant MT-9315 and by a Kidney Foundation of
Canada grant (to G. N. H.)The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a doctoral fellowship from the CIHR and a National
Cancer Institute of Canada research studentship.
§
To whom correspondence should be addressed: Calcium Research
Laboratory, Rm. H4.67, Royal Victoria Hospital, 687 Pine Ave. W.,
Montreal, Quebec H3A 1A1, Canada. Tel.: 514-843-1632; Fax: 514-843-1712; E-mail: geoffrey.hendy@mcgill.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. E C Cole, F. H J Yun, B. Y L Wong, A. Y Shuen, R. A Booth, A. Scillitani, S. Pidasheva, X. Zhou, L. Canaff, and G. N Hendy Calcium-sensing receptor mutations and denaturing high performance liquid chromatography J. Mol. Endocrinol., April 1, 2009; 42(4): 331 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Saidak, R. Mentaverri, and E. M. Brown The Role of the Calcium-Sensing Receptor in the Development and Progression of Cancer Endocr. Rev., April 1, 2009; 30(2): 178 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bikle Nonclassic Actions of Vitamin D J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 26 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Taniguchi, M. Tokumoto, K. Tsuruya, H. Hirakata, and M. Iida Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3662 - 3669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Carrillo-Lopez, D. Alvarez-Hernandez, I. Gonzalez-Suarez, P. Roman-Garcia, J. M. Valdivielso, J. L. Fernandez-Martin, and J. B. Cannata-Andia Simultaneous changes in the calcium-sensing receptor and the vitamin D receptor under the influence of calcium and calcitriol Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3479 - 3484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Dong, C. M. Ulrich, L. Hsu, D. J. Duggan, D. S. Benitez, E. White, M. L. Slattery, B. J. Caan, J. D. Potter, and U. Peters Genetic Variation in Calcium-Sensing Receptor and Risk for Colon Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2755 - 2765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Canaff, X. Zhou, and G. N. Hendy The Proinflammatory Cytokine, Interleukin-6, Up-regulates Calcium-sensing Receptor Gene Transcription via Stat1/3 and Sp1/3 J. Biol. Chem., May 16, 2008; 283(20): 13586 - 13600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1{alpha} PNAS, February 19, 2008; 105(7): 2598 - 2603.
|
|
|
|
|
|
T. Drueke, D. Martin, and M. Rodriguez Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1828 - 1839. [Full Text] [PDF]
|
|
|
|
|
|
K. Zajickova, J. Vrbikova, L. Canaff, P. D. Pawelek, D. Goltzman, and G. N. Hendy Identification and Functional Characterization of a Novel Mutation in the Calcium-Sensing Receptor Gene in Familial Hypocalciuric Hypercalcemia: Modulation of Clinical Severity by Vitamin D Status J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2616 - 2623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wesseling and I. B. Salusky Current treatment options in secondary hyperparathyroidism Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2986 - 2987. [Full Text] [PDF]
|
|
|
|
|
|
Y. Cui and T. E. Rohan Vitamin d, calcium, and breast cancer risk: a review. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1427 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Mittelman, G. N. Hendy, R. A. Fefferman, L. Canaff, I. Mosesova, D. E. C. Cole, L. Burkett, and M. E. Geffner A Hypocalcemic Child with a Novel Activating Mutation of the Calcium-Sensing Receptor Gene: Successful Treatment with Recombinant Human Parathyroid Hormone J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2474 - 2479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Diorio, S. Berube, C. Byrne, B. Masse, N. Hebert-Croteau, M. Yaffe, G. Cote, M. Pollak, and J. Brisson Influence of Insulin-like Growth Factors on the Strength of the Relation of Vitamin D and Calcium Intakes to Mammographic Breast Density Cancer Res., January 1, 2006; 66(1): 588 - 597. [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]
|
|
|
|
 |
|
 J. J. Yao, S. Bai, A. J. Karnauskas, D. A. Bushinsky, and M. J. Favus Regulation of Renal Calcium Receptor Gene Expression by 1,25-Dihydroxyvitamin D3 in Genetic Hypercalciuric Stone-Forming Rats J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1300 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Canaff and G. N. Hendy Calcium-sensing Receptor Gene Transcription Is Up-regulated by the Proinflammatory Cytokine, Interleukin-1{beta}: ROLE OF THE NF-{kappa}B PATHWAY AND {kappa}B ELEMENTS J. Biol. Chem., April 8, 2005; 280(14): 14177 - 14188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Forsberg, E. Bjorck, J. Hashemi, J. Zedenius, A. Hoog, L.-O. Farnebo, M. Reimers, and C. Larsson Distinction in gene expression profiles demonstrated in parathyroid adenomas by high-density oligoarray technology Eur. J. Endocrinol., March 1, 2005; 152(3): 459 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wystrychowski, S. Pidasheva, L. Canaff, J. Chudek, F. Kokot, A. Wiecek, and G. N. Hendy Functional Characterization of Calcium-Sensing Receptor Codon 227 Mutations Presenting as Either Familial (Benign) Hypocalciuric Hypercalcemia or Neonatal Hyperparathyroidism J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 864 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez, E. Nemeth, and D. Martin The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism Am J Physiol Renal Physiol, February 1, 2005; 288(2): F253 - F264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chakrabarty, H. Wang, L. Canaff, G. N. Hendy, H. Appelman, and J. Varani Calcium Sensing Receptor in Human Colon Carcinoma: Interaction with Ca2+ and 1,25-Dihydroxyvitamin D3 Cancer Res., January 15, 2005; 65(2): 493 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shiizaki, S. Negi, I. Hatamura, T. Sakaguchi, F. Saji, K. Kunimoto, M. Mizobuchi, I. Imazeki, A. Ooshima, and T. Akizawa Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats J. Am. Soc. Nephrol., January 1, 2005; 16(1): 97 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Peters, N. Chatterjee, M. Yeager, S. J. Chanock, R. E. Schoen, K. A. McGlynn, T. R. Church, J. L. Weissfeld, A. Schatzkin, and R. B. Hayes Association of Genetic Variants in the Calcium-Sensing Receptor with Risk of Colorectal Adenoma Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2181 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mizobuchi, I. Hatamura, H. Ogata, F. Saji, S. Uda, K. Shiizaki, T. Sakaguchi, S. Negi, E. Kinugasa, S. Koshikawa, et al. Calcimimetic Compound Upregulates Decreased Calcium-Sensing Receptor Expression Level in Parathyroid Glands of Rats with Chronic Renal Insufficiency J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2579 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Chen and W. G. Goodman Role of the calcium-sensing receptor in parathyroid gland physiology Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1005 - F1011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Grau, J. A. Baron, R. S. Sandler, R. W. Haile, M. L. Beach, T. R. Church, and D. Heber Vitamin D, Calcium Supplementation, and Colorectal Adenomas: Results of a Randomized Trial J Natl Cancer Inst, December 3, 2003; 95(23): 1765 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. N. Hendy, C. Minutti, L. Canaff, S. Pidasheva, B. Yang, Z. Nouhi, D. Zimmerman, C. Wei, and D. E. C. Cole Recurrent Familial Hypocalcemia Due to Germline Mosaicism for an Activating Mutation of the Calcium-Sensing Receptor Gene J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3674 - 3681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Iwasaki, T. Kakuta, H. Haruguchi, N. Fukuda, K. Kurokawa, and M. Fukagawa Adenovirus-mediated functional gene transfer into parathyroid cells in vivo and in vitro Nephrol. Dial. Transplant., March 1, 2003; 18(90003): iii18 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nakanishi, S. Yano, R. Nomura, T. Tsukamoto, Y. Shimizu, J. Shin, and M. Fukagawa Efficacy of direct injection of calcitriol into the parathyroid glands in uraemic patients with moderate to severe secondary hyperparathyroidism Nephrol. Dial. Transplant., March 1, 2003; 18(90003): iii47 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Tryfonidou, M. A. Oosterlaken-Dijksterhuis, J. A. Mol, T. S. G. A. M. van den Ingh, W. E. van den Brom, and H. A. W. Hazewinkel 24-Hydroxylase: potential key regulator in hypervitaminosis D3 in growing dogs Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E505 - E513. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |