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Sulforaphane and trichostatin A histone deacetylase inhibitors increase vitamin D‐induced CYP24 expression in intestinal cells
Author(s) -
Muriithi Caroline,
Larnard Jeffrey,
Wood Richard J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb278
Subject(s) - trichostatin a , histone deacetylase , chemistry , calcitriol receptor , histone deacetylase inhibitor , microbiology and biotechnology , gene expression , histone , vitamin d and neurology , epigenetics , activator (genetics) , cancer research , biology , biochemistry , endocrinology , gene
Epigenetic changes, such as acetylation of nuclear histone proteins, can be induced by bioactive food components and alter chromatin structure and the expression of certain genes. Sulforaphane (SFN) and trichostatin A (TSA) have histone deacetylase inhibitor (HDACI) activity. We hypothesized that HDACI treatment would increase vitamin D‐induced CYP24 and TRPV6 gene expression. We tested the effect of four dosages of SFN (1, 2.5, 5 and 10 μmol/L) and one dose of TSA (1 μmol/L) with and without the presence of 10 nmol/L 1, 25‐dihydroxyvitamin D (1, 25 (OH)2D) for 24h on the expression of CYP24 and TRPV6 in the Caco‐2 human intestinal cell model. Western blot analysis showed an increase in the protein expression levels of CYP24 with SFN and 1,25 (OH)2D. Realtime qPCR was used to calculate the relative change in mRNA expression of CYP24 and TRPV6. TSA alone increased (p<.05) CYP24 mRNA expression. 1,25 (OH)2D increased CYP24 and TRPV6 mRNA expression in Caco‐2 cells. TSA also increased vitamin D‐induced CYP24 mRNA expression, but vitamin D‐induced TRPV6 expression was not affected by HDACI treatment. Our results demonstrate that HDACIs can differentially affect the expression of certain vitamin D‐dependent genes in Caco‐2 intestinal cells. Additional studies are needed to determine HDACI effects on vitamin D‐related functions in vivo. This work was supported by a Massachusetts Experiment Station HATCH grant MAS000902