From: Kofi on
No doubt this accelerated breakdown of vitamin D by smoking metabolites
helps to account for the adverse effects of smoking on other conditions
like Crohn's. In essence, smoking is chewing up your vitamin D stores.

Toxicol Sci. 2009 May;109(1):50-8. Epub 2009 Feb 25

The aryl hydrocarbon receptor activator benzo[a]pyrene enhances vitamin
D3 catabolism in macrophages.
Matsunawa M, Amano Y, Endo K, Uno S, Sakaki T, Yamada S, Makishima M.
Division of Biochemistry, Department of Biomedical Sciences, Nihon
University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon produced by
cigarette combustion, is implicated as a causative agent in
smoking-related cancer and atherosclerosis. 1,25-Dihydroxyvitamin D3
[1,25(OH)2D3], a potent ligand for the nuclear receptor vitamin D
receptor (VDR), has been shown to decrease the risk of osteoporosis,
some types of cancer and cardiovascular disease, suggesting an opposing
effect of vitamin D3 to cigarette smoking. In this study, we
investigated the effects of BaP on the vitamin D3 signaling pathway. BaP
effectively enhanced the 1,25(OH)2D3-dependent induction of cytochrome
P450 24A1 (CYP24A1) in human monocyte/macrophage-derived THP-1 cells and
breast cancer MCF-7 cells. BaP combination was less or not effective on
mRNA expression of CD14, arachidonate 5-lipoxygenase, and cathelicidin
antimicrobial peptide in THP-1 cells. BaP also increased the expression
of CYP24A1 induced by a non-vitamin D VDR ligand, lithocholic acid
acetate. Another aryl hydrocarbon receptor (AhR) ligand,
2,3,7,8-tetrachlorodibenzo-p-dioxin, enhanced CYP24A1 expression by
1,25(OH)2D3 in THP-1 cells. Treatment of cells with an AhR antagonist
and a protein synthesis inhibitor inhibited the enhancing effect of BaP
on CYP24A1 induction, indicating that the effects of BaP are mediated by
AhR activation and de novo protein synthesis. BaP pretreatment increased
1,25(OH)2D3-dependent recruitment of VDR and retinoid X receptor to the
CYP24A1 promoter. Analysis of 1,25(OH)2D3 metabolism showed that BaP
enhanced the hydroxylation of 1,25(OH)2D3 by CYP24A1 in THP-1 cells.
Thus, AhR activation by BaP stimulates vitamin D3 catabolism. Modulation
of vitamin D signaling by AhR may represent a mechanism underlying
cigarette smoking-related diseases.

Publication Types:
* Research Support, Non-U.S. Gov't

PMID: 19244278
From: Dr. DRErnie on
"Kofi" <kofi(a)anon.un> wrote in message
news:kofi-EBB321.00393822112009(a)news.west.earthlink.net...
> No doubt this accelerated breakdown of vitamin D by smoking metabolites
> helps to account for the adverse effects of smoking on other conditions
> like Crohn's. In essence, smoking is chewing up your vitamin D stores.
>
> Toxicol Sci. 2009 May;109(1):50-8. Epub 2009 Feb 25
>
> The aryl hydrocarbon receptor activator benzo[a]pyrene enhances vitamin
> D3 catabolism in macrophages.
> Matsunawa M, Amano Y, Endo K, Uno S, Sakaki T, Yamada S, Makishima M.
> Division of Biochemistry, Department of Biomedical Sciences, Nihon
> University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.
>
> Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon produced by
> cigarette combustion, is implicated as a causative agent in
> smoking-related cancer and atherosclerosis. 1,25-Dihydroxyvitamin D3
> [1,25(OH)2D3], a potent ligand for the nuclear receptor vitamin D
> receptor (VDR), has been shown to decrease the risk of osteoporosis,
> some types of cancer and cardiovascular disease, suggesting an opposing
> effect of vitamin D3 to cigarette smoking. In this study, we
> investigated the effects of BaP on the vitamin D3 signaling pathway. BaP
> effectively enhanced the 1,25(OH)2D3-dependent induction of cytochrome
> P450 24A1 (CYP24A1) in human monocyte/macrophage-derived THP-1 cells and
> breast cancer MCF-7 cells. BaP combination was less or not effective on
> mRNA expression of CD14, arachidonate 5-lipoxygenase, and cathelicidin
> antimicrobial peptide in THP-1 cells. BaP also increased the expression
> of CYP24A1 induced by a non-vitamin D VDR ligand, lithocholic acid
> acetate. Another aryl hydrocarbon receptor (AhR) ligand,
> 2,3,7,8-tetrachlorodibenzo-p-dioxin, enhanced CYP24A1 expression by
> 1,25(OH)2D3 in THP-1 cells. Treatment of cells with an AhR antagonist
> and a protein synthesis inhibitor inhibited the enhancing effect of BaP
> on CYP24A1 induction, indicating that the effects of BaP are mediated by
> AhR activation and de novo protein synthesis. BaP pretreatment increased
> 1,25(OH)2D3-dependent recruitment of VDR and retinoid X receptor to the
> CYP24A1 promoter. Analysis of 1,25(OH)2D3 metabolism showed that BaP
> enhanced the hydroxylation of 1,25(OH)2D3 by CYP24A1 in THP-1 cells.
> Thus, AhR activation by BaP stimulates vitamin D3 catabolism. Modulation
> of vitamin D signaling by AhR may represent a mechanism underlying
> cigarette smoking-related diseases.
>
> Publication Types:
> * Research Support, Non-U.S. Gov't
>
> PMID: 19244278

Smoking gets more nutrients to the hairy one. Ernie