Vitamin D-dependent rickets type II. Defective induction of 25-hydroxyvitamin D3-24-hydroxylase by 1,25-dihydroxyvitamin D3 in cultured skin fibroblasts.

Gamblin, George T.; Liberman, Uri; Eil, Charles; Downs, Robert W.; DeGrange, D A; Marx, Stephen J.

doi:10.1172/jci111796

Cited by 84 publications

(31 citation statements)

References 46 publications

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“…VDDR II is also inherited as an autosomal recessive trait, and exhibits the almost same clinical features as the VDDR I patients, but unlike VDDR I, serum levels of 1α,25(OH) 2 D 3 are high in the VDDR II patients. The physiological doses of 1α,25(OH) 2 D 3 are unable to rescue the rachitic abnormality [19], suggesting that the VDDR II patients lack physiological response to [21]. Alopecia is seen only in some VDDR II patients, and supposed to be a best symptom to distinguish from the other rickets.…”

Section: Vitamin D-dependent Hereditary Ricketsmentioning

confidence: 99%

Molecular Genetics of Vitamin D- Dependent Hereditary Rickets

et al. 2002

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Vitamin D exerts a wide variety of biological actions. The active form of vitamin D, 1α,25(OH)₂D₃, is biosynthesized from cholesterol. The final, critical step in this biosynthesis is conversion from 25-hydroxyvitamin D₃ to 1α,25(OH)₂D₃ by the enzyme 25-hydroxyvitamin D₃ 1α-hydroxylase(CYP27B1)[1α(OH)ase]. 1α,25(OH)₂D₃ transcriptionally controls the expression of a particular set of target genes mediated through nuclear vitamin D receptor(VDR) acting as a ligand-inducible factor. Two types of vitamin D-dependent hereditary rickets (VDDR) are known to be caused by mutations in the 1α(OH)ase and VDR genes. The 1α(OH)ase gene is responsible for VDDR type I, and VDR for type II. Both of the diseases display an autosomal-recessive trait, but clinical features and response to administrated 1α,25(OH)₂D₃ are distinct. The phenotypes of the gene KO mice deficient of 1α(OH)ase and VDR exhibited the clinical abnormalities observed in the VDDR patients.

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Section: Vitamin D-dependent Hereditary Ricketsmentioning

confidence: 99%

Molecular Genetics of Vitamin D- Dependent Hereditary Rickets

et al. 2002

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“…Briefly, after HL-60 cells were cultured in a medium containing 10% normal or uremic serum for the indicated times, the cells were inoculated at 2.0 x I06 cells/ml. After treatment with the indicated concentrations of 1,25-(OH)2Dj for 24 h, the cells were subjected to a vitamin D, 'washoutprocedure [25] to remove added vitamin D, compound which might compete with l,25-(OH)2[26,27-'H]D3 for the substrate site on the 4,000 dpm/pm ol) and incubated at 37 °C for 3 h in a shaking water bath. The reaction was stopped by the addition of 0.3 ml of 0.1 /V acetic acid, followed by the addition of 0.5 ml of saturated sodium periodate.…”

Section: Preparation O F Hl-60 Cel! Extractmentioning

confidence: 99%

Effect of Uremic Serum on 1,25-Dihydroxyvitamin D<sub>3</sub>-lnduced Differentiation of Human Promyelocytic Leukemia Cell, HL-60

Inaba

Okuno²,

Koyama³

et al. 1993

Nephron

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The mechanism by which resistance to 1,25-(OH)₂D₃ occurs in patients with chronic renal failure was studied. 1,25-(OH)₂D₃ causes the induction of differentiation and of 1,25-(OH)₂D₃-24-hydroxylase activity in the mitochondria of the human promyelocytic leukemia cell line, HL-60, via a steroid hormone-receptor mechanism. Treatment of these cells with 10 ⁸M 1,25-(OH)₂D₃ for 5 days in a medium containing 10% uremic serum from 4 patients with chronic renal failure resulted in maturation of the cells amounting to 30.3 ± 18.7 (mean ± SD) and 32.5 ± 11.2% maturation by the nitroblue tetrazolium reduction assay and the nonspecific esterase assay, respectively. These values were significantly lower than those obtained with 10% normal serum from 3 normal controls (66.6 ± 12.8 and 58.3 ± 10.9%, p < 0.02). The occurrence of resistance to 1,25-(OH)₂D₃ in uremic serum-treated cells was also confirmed when the effect of 1,25-(OH)₂D₃was assessed by the induction of the cell’s ability to hydroxylate the C-24 position of 1,25-(OH)₂[³H]D₃. Treatment of HL-60 cells with a mixture of 5% uremic plus 5% normal serum impaired 1,25-(OH)₂D₃-induced cell differentiation to the levels as those in 10% uremic serum, strongly suggesting the occurrence of a substance(s) having 1,25-(OH)₂D₃-inhibitory activity in the uremic serum. A significant reduction in 1,25-(OH)₂D₃ receptor levels was observed in uremic serum-treated cells. We have recently reported that the addition of dibutyryl cAMP significantly enhances the effect of l,25-(OH)₂D₃ on HL-60 cells by increasing 1,25-(OH)₂D₃ receptor levels and that a significant positive correlation was observed between intracellular cAMP levels and 1,25-(OH)₂D₃-induced HL-60 cell maturation. Together with the data that treatment of the cells with uremic serum resulted in a significant reduction in intracellular cAMP levels, the significance of cAMP in the occurrence of 1,25-(OH)₂D₃-resistance in uremic serum-treated cells is indicated.

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“…Hereditary 1,25-dihydroxyvitamin D resistant rickets (HVDRR), also known as vitamin D-dependent rickets, type II, is an autosomal recessive disorder that has been shown to be caused by mutations in the VDR (1,2). The disease is characterized by early onset rickets, hypocalcemia, secondary hyperparathyroidism, elevated 1,25(OH) 2 D 3 levels, and resistance to 1,25(OH) 2 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In the receptor positive cases the VDR was shown to exhibit a decreased binding affinity for DNA.…”

Section: Introductionmentioning

confidence: 99%