Fiche publication
Date publication
mai 2024
Journal
Biomolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHEL-GUIBERTEAU Natacha
,
Dr LAVERNY Gilles
,
Dr OSZ-PAPAI Judit
Tous les auteurs :
Peluso-Iltis C, Pierrat N, Rovito D, Osz J, Sawada D, Kittaka A, Laverny G, Rochel N
Lien Pubmed
Résumé
The active vitamin D metabolites, 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D is a major one. This study aims to investigate the structure-activity relationships of 4-hydroxy derivatives of 1,25D. Structural analysis indicates that 1,4α,25(OH)D and 1,4β,25(OH)D maintain the anchoring hydrogen bonds of 1,25D and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D and 1,4β,25D are as potent as 1,25D in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound.
Mots clés
calcemia, structure–function, synthesis, vitamin D metabolites
Référence
Biomolecules. 2024 05 3;14(5):
