Parathyroid hormone activation of the 25-hydroxyvitamin D3-1α-hydroxylase gene promoter

被引:182
作者
Brenza, HL
Kimmel-Jehan, C
Jehan, F
Shinki, T
Wakino, S
Anazawa, H
Suda, T
DeLuca, HF
机构
[1] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA
[2] Showa Univ, Sch Dent, Dept Biochem, Shinagawa Ku, Tokyo 142, Japan
[3] Keio Univ, Dept Internal Med, Shinjuku Ku, Tokyo 160, Japan
[4] Kyowa Hakko Kogyo Co Ltd, Tokyo Res Labs, Tokyo 194, Japan
关键词
vitamin D; calcium; bone; kidney; cyclic AMP;
D O I
10.1073/pnas.95.4.1387
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The DNA flanking the 5' sequence of the mouse 1 alpha-hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activity has br!en demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroid hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of parathyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D-3 does not suppress basal promoter activity and marginally suppresses parathyroid hormone-driven luciferase reporter activity. The promoter has three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results indicate that parathyroid hormone stimulates 25-hydroxyvitamin D-3-1 alpha-hydroxylase by acting on the promoter of the 1 alpha-hydroxylase gene.
引用
收藏
页码:1387 / 1391
页数:5
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