Proteins in the heat shock 70 family specifically bind 25-hydroxyvitamin D3 and 17β-estradiol

被引:31
作者
Gacad, MA
Adams, JS
机构
[1] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Endocrinol & Metab, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Burns & Allen Res Inst, Los Angeles, CA 90048 USA
关键词
D O I
10.1210/jc.83.4.1264
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Most New World primates evolved to express a form of compensated resistance to steroid hormones from the gonads and adrenal glands as well as to the hydroxylated vitamin D-S prohormone, 25-hydroxyvitamin D-3 (25OHD(3)), and the vitamin D hormone 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] originating from the liver and kidney, respectively. We recently demonstrated that this farm of resistance is associated with the overexpression of a novel member of the 70-kDa heat shock protein (hsp-70) molecular chaperone family, which we have termed the intracellular vitamin D binding protein (IDBP). In the current report we more closely examine the ligand-binding capability of purified IDBP and two other mammalian hsp-70 family members, heat-inducible (hsp-70) and constitutively expressed (hsc-70) hsp-70 proteins. Purified IDBP, hsp-70, and hsc-70 all bound 25OHD(3) with relatively high affinity; the mean K-d for 25OHD(3) ranged from 0.5-2.2 nmol/L (rank order: IDBP greater than or equal to hsp-70 greater than or equal to hsc-70). By Scatchard analysis, high affinity, specific binding of 1,25-(OH)(2)D-3 was not reproducibly observed for any of the three members of the hsp-70 family. Unlike purified IDBP, hsc-70 and hsp-70 were also competent binders of the gonadal steroid 17 beta-estradiol (mean K-d for 25OHD(3), 2.5 and 6.6 nmol/L by hsc-70 and hsp-70, respectively), but not of two other gonadal hormones, progesterone and testosterone. These data suggest that IDBP is relatively specific for 25OHD(3) and that additional hsp-70-like binding proteins are present in unpurified New World primate cell extracts that are specific for 1-hydroxylated vitamin D metabolites as well as other gonadal steroid hormones.
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页码:1264 / 1267
页数:4
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