An Essential Role of the CAAT/Enhancer Binding Protein-α in the Vitamin D-Induced Expression of the Human Steroid/Bile Acid-Sulfotransferase (SULT2A1)

Song, Chung S.; Echchgadda, Ibtissam; Seo, Young Kyo; Oh, Taesung; Kim, Soyoung; Kim, Sung‐A; Cho, Sung-Hwan; Shi, Liheng; Chatterjee, Bandana

doi:10.1210/me.2005-0428

Cited by 39 publications

(34 citation statements)

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“…The identified IR2 in this report agrees with a previous prediction of several putative (A/G)G(G/T)TCA nuclear receptor half-site motifs in the 5′-flanking region of hSULT2A1 (Duanmu et al, 2002). Our results also agree with a recent report on VDR mediated bile acid induction of hSULT2A1 through interaction with CAAT/ Enhancer Binding Protein-alpha (C/EBPα) (Song et al, 2005).…”

Section: Discussionsupporting

confidence: 93%

“…Peroxisome proliferator-activated receptor alpha (PPARα) was also found to involve in the transcriptional regulation of hSULT2A1 through the DNA response element located in -5949 to -5929 upstream of the promoter region (Fang et al, 2005). The vitamin D receptor (VDR) was reported to target hSULT2A1 promoter through interaction with CAAT/Enhancer Binding Protein-alpha (C/EBPα) (Song et al, 2006). Methotrexate (MTX) is a widely used drug against cancer and other diseases (Walling, 2006,Green et al, 2006.…”

Section: Introductionmentioning

confidence: 99%

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Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1)☆

et al. 2007

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Sulfotransferases (SULTs) catalyzed sulfation is important in the regulation of biological activities of hormones and neurotransmitters, the metabolism of drugs, and the detoxification of xenobiotic toxicants. Sulfation also leads to the bioactivation of procarcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) is a major SULT catalyzing the sulfation of hydroxysteroids and xenobiotic alcohols. Our previous studies had shown that the anti-folate drug methotrexate (MTX) can up-regulate several major isoforms of human SULTs. To determine the mechanisms controlling the regulation of hSULT2A1, the 5′-flanking region of hSULT2A1 was constructed into the pGL3-Basic luciferase reporter vector. The transcriptional regulation mechanism of hSULT2A1 promoter was studied using Caco-2 cell line based on the reporter gene assay. Nuclear receptor co-transfection results indicated that human constitutive androstane receptor (hCAR) and human retinoid X receptor α (hRXRα) were involved in the transcriptional regulation of hSULT2A1. RNA interference experiments further proved the role of hCAR in hSULT2A1 regulation. Progressive promoter deletion, DNA sequence alignment, and site directed promoter mutation results suggested that an imperfect inverted repeat DNA motif, IR2 (-186AGCTCAGATGACCC-173), within the hSULT2A1 promoter region mediated the hSULT2A1 induction by MTX. Furthermore, electrophoretic mobility shift assay and super shift assay were employed to characterize the interactions of hCAR and hRXRα with the IR2 element. In summary, we identified an IR2 DNA cis-element located at -186/-173 of hSULT2A1 promoter region; the IR2 element mediates the MTX induction of hSULT2A1 through interacting with hCAR and hRXRα.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1)☆

et al. 2007

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“…We had shown earlier that the vitamin D 3 -and xenobiotic-mediated induction of the mouse Sult2A1 promoter in transfected liver and intestinal cells is dependent upon binding of the corresponding receptors to a 21-base pair inverted repeat (IR0) enhancer (Echchgadda et al, 2004b). Chromatin immunoprecipitation (ChIP) assay showed that the IR0 in the Sult2A1 chromatin was enriched for VDR in the livers of vitamin D 3 -injected mice, thus validating the enhancer's role in a tissue context (Song et al, 2006). In the present report we show that aging has no significant influence on the qualitative and quantitative profiles of the Sult2A1 mRNA induction by vitamin D 3 or PCN.…”

Section: Introductionmentioning

confidence: 83%

“…In the present study young and old mice were examined for the induced expression of the phase II sulfotransferase SULT2A1 in the liver upon administration of the synthetic catatoxic steroid PCN (pregnenolone-16α-carbonitrile), which is an agonist ligand for PXR, or vitamin D 3 , which binds and activates the vitamin D receptor (VDR). Vitamin D 3 has a known role in xenobiotic metabolism in addition to its classic function in bone physiology (Makishima et al 2002;Reschly and Krasowski, 2006;Song et al, 2006). Additionally, we probed the mouse liver chromatin to investigate the association of nuclear receptors and coregulators with a vitamin D-and xenobiotic-responsive enhancer in the Sult2A1 promoter.…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme is expressed at high abundance in the first-pass tissues (liver and intestine) and in the steroidogenic tissue of the adrenal gland. Multiple nuclear receptors including PXR, CAR and VDR can induce SULT2A1 in cultured cells and in vivo in the mouse liver (Song et al, 2001;Sonoda et al, 2002;Echchgadda et al, 2004a;Assem et al, 2004;Maglich et al, 2004;Fang et al, 2005;Seeley et al, 2005;Chatterjee et al, 2005;Song et al, 2006). We had shown earlier that the vitamin D 3 -and xenobiotic-mediated induction of the mouse Sult2A1 promoter in transfected liver and intestinal cells is dependent upon binding of the corresponding receptors to a 21-base pair inverted repeat (IR0) enhancer (Echchgadda et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

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Xenobiotic- and vitamin D-responsive induction of the steroid/bile acid-sulfotransferase Sult2A1 in young and old mice: The role of a gene enhancer in the liver chromatin

Seo

Chung

Kim

et al. 2007

Gene

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The xenobiotic-activated nuclear receptors PXR (pregnane X receptor) and CAR (constitutive androstane receptor) and the vitamin D 3 -activated nuclear receptor VDR regulate steroid and xenobiotic metabolism by inducing the phase I cytochrome P450 monooxygenases, phase II conjugating transferases, and the phase III transporters, which mediate the efflux of water-soluble lipid metabolites from cells. Metabolic stress due to the deviant expression of steroid-and xenobioticmetabolizing enzymes is known to have severe health consequences including accelerated aging, and increased expression of these enzymes is associated with extended longevity (Gachon et al, 2006;McElwee et al, 2004). Information on the similarities and dissimilarities in drug metabolism between the young and old, as may be uncovered by studying aging regulation of the genes relevant to steroid and xenobiotic metabolism, is likely to have clinical significance. In this report, we examined the VDR-and PXR-mediated gene induction of the phase II sulfotransferase Sult2A1 in the livers of 4-month and 20-month old mice. Sult2A1 converts bile acids, steroids and a number of drugs to the corresponding sulfated metabolites, which are readily eliminated from the body due to increased water solubility. In RT-PCR assay, aging did not change the induction of Sult2A1 mRNAs by the hormonally active vitamin D 3 and the catatoxic synthetic steroid PCN (pregnenolone-16α-carbonitrile). Chromatin immunoprecipitation (ChIP) from liver nuclei showed that aging had no effect on the activity of an IR0 enhancer in the Sult2A1 chromatin to recruit VDR, RXR-α (retinoid X receptor) and PXR in mice injected with D 3 or PCN. Thus, mice in late life are as competent as those in early life in responding to the hormonal and xenobiotic signaling for Sult2A1 induction. This is the first report describing the role of aging in the functional response of an enhancer in the liver chromatin to the nuclear receptor-dependent signaling.

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The Biochemistry of Drug Metabolism – An Introduction

Krämer

Testa

2009

Chemistry & Biodiversity

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This review on intra-individual factors affecting drug metabolism completes our series on the biochemistry of drug metabolism. The article presents the molecular mechanisms causing intra-individual differences in enzyme expression and activity. They include enzyme induction by transcriptional activation and enzyme inhibition on the protein level. The influencing factors are of physiological, pathological, or external origin. Tissue characteristics and developmental age strongly influence enzyme-expression patterns. Further influencing factors are pregnancy, disease, or biological rhythms. Xenobiotics, drugs, constituents of herbal remedies, food constituents, ethanol, and tobacco can all influence enzyme expression or activity and, hence, affect drug metabolism.

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An Essential Role of the CAAT/Enhancer Binding Protein-α in the Vitamin D-Induced Expression of the Human Steroid/Bile Acid-Sulfotransferase (SULT2A1)

Cited by 39 publications

References 43 publications

Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1)☆

Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1)☆

Xenobiotic- and vitamin D-responsive induction of the steroid/bile acid-sulfotransferase Sult2A1 in young and old mice: The role of a gene enhancer in the liver chromatin

The Biochemistry of Drug Metabolism – An Introduction

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