Isolation of a new metabolite of vitamin D produced in vivo, 1α,25-dihydroxyvitamin D3-26,23-lactone

Ohnuma, Norio; Bannai, Kiyoshi; Yamaguchi, Hisao; Hashimoto, Yoshiro; Norman, Anthony W.

doi:10.1016/0003-9861(80)90047-8

Cited by 57 publications

(13 citation statements)

References 12 publications

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“…These changes in circulating calcium could have contributed to decreased renal 1-hydroxylase activity [25]. partitioning of 1,25(OH)2D3 metabolites into a basic aqueous phase of water-methanol-chloroform extraction system identical to the one used in our studies, and Ohnuma et al [28] isolated from rats a lactone-derivative metabolite of 1,25(OH)2D3 that is also more polar than the parent substance.…”

Section: Discussionmentioning

confidence: 98%

Acquired alterations in vitamin D metabolism in the acidotic state

Baran

Lee

et al. 1982

Calcif Tissue Int

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Classic (type I) renal tubular acidosis in children in attended by growth retardation and rickets, abnormalities that can be corrected by alkali therapy alone. We have employed the NH4Cl-treated rachitic chick as a model to investigate vitamin D metabolism in the acidotic state. NH4Cl ingestion for 96 h was associated with a rise in serum calcium, a significant decrease in blood pH (7.42 +/- 0.08 vs 7.30 +/- 0.08, P less than 0.005), decreased [3H]1,25(OH)2D3 following [3H]25OHD D3 injections, and enhanced metabolic clearance of administered [3H]1,25(OH)2D3. The data collectively suggest that metabolic acidosis in the chick alters the production and degradation of 1,25(OH)2D3.

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Section: Discussionmentioning

confidence: 98%

Acquired alterations in vitamin D metabolism in the acidotic state

Baran

Lee

et al. 1982

Calcif Tissue Int

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“…1,25-lactone has been isolated and identified as a metabolite of 1,25(OH) 2 D 3 in sera from animals administered pharmacologic doses of 1,25(OH) 2 D 3 , as well as from humans under physiological conditions (57,58). Although the precise metabolic half-life of 1,25-lactone has not been determined, it appears to be longer than that of 1,25(OH) 2 D 3 (59).…”

Section: Figurementioning

confidence: 99%

A nonclassical vitamin D receptor pathway suppresses renal fibrosis

et al. 2013

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The TGF-β superfamily comprises pleiotropic cytokines that regulate SMAD and non-SMAD signaling. TGF-β-SMAD signal transduction is known to be involved in tissue fibrosis, including renal fibrosis. Here, we found that 1,25-dihydroxyvitamin D 3 -bound [1,25(OH) 2 D 3 -bound] vitamin D receptor (VDR) specifically inhibits TGF-β-SMAD signal transduction through direct interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH) 2 D 3 treatment prevented renal fibrosis through the suppression of TGF-β-SMAD signal transduction. Based on the structure of the VDR-ligand complex, we generated 2 synthetic ligands. These ligands selectively inhibited TGF-β-SMAD signal transduction without activating VDR-mediated transcription and significantly attenuated renal fibrosis in mice. These results indicate that 1,25(OH) 2 D 3 -dependent suppression of TGF-β-SMAD signal transduction is independent of VDR-mediated transcriptional activity. In addition, these ligands did not cause hypercalcemia resulting from stimulation of the transcriptional activity of the VDR. Thus, our study provides a new strategy for generating chemical compounds that specifically inhibit TGF-β-SMAD signal transduction. Since TGF-β-SMAD signal transduction is reportedly involved in several disorders, our results will aid in the development of new drugs that do not cause detectable adverse effects, such as hypercalcemia.

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“…[l]; and 1~,25-(OH)~D~-26,23-lactone [2,3]. The stereochemistry of both metabolites is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Although 4 possible diastereoisomers of 25-OH-D3-26,23-lactone have been synthesized [4-81, they have not been directly compared to the natural metabolite. We have reported the isolation of a new metabolite, DA and proposed that its structure was tentatively determined to be la,25 (OH)zD3-26,23-lactone without measurement of IR spectrum [3]. were chemically synthesized as in [7,8].…”

Section: Introductionmentioning

confidence: 99%