20-hydroxycholecalciferol, product of vitamin d3 hydroxylation by p450scc, decreases nf-κb activity by increasing iκbα levels in human keratinocytesp450scc 20-hydroxycholecalciferol,维生素d3的产物羟基化,减少nf-κb活动增加iκbα人类角质细胞水平.pdfVIP
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20-hydroxycholecalciferol, product of vitamin d3 hydroxylation by p450scc, decreases nf-κb activity by increasing iκbα levels in human keratinocytesp450scc 20-hydroxycholecalciferol,维生素d3的产物羟基化,减少nf-κb活动增加iκbα人类角质细胞水平
20-Hydroxycholecalciferol, Product of Vitamin D3
Hydroxylation by P450scc, Decreases NF-kB Activity by
Increasing IkBa Levels in Human Keratinocytes
1 1 2 1 2
Zorica Janjetovic , Michal A. Zmijewski , Robert C. Tuckey , Damon A. DeLeon , Minh N. Nguyen ,
1 1
Lawrence M. Pfeffer , Andrzej T. Slominski *
1 Department of Pathology and Laboratory Medicine, the Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, United States
of America, 2 School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Australia
Abstract
The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1) to form 20-
hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal
keratinocytes. Since nuclear factor-kB (NF-kB) plays a pivotal role in the regulation of cell proliferation, differentiation and
apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kB, using 1,25-
dihydroxycholecalciferol (calcitriol) as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkB DNA
binding activity as well as NF-kB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced
significant increases in the mRNA and protein levels of the NF-kB inhibitor protein, IkBa, in a time dependent manner, while
no changes in total NF-kB-p65 mRNA or protein levels were observed. Another measure of NF-kB activity, p65 translocation
from the cytoplasm into the nucleus was also
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