DP97, a DEAD box DNA/RNA helicase, is a target gene-selective co-regulator of the constitutive androstane receptor

Kanno, Yuichiro; Serikawa, Takafumi; Inajima, Jun; Inouye, Yoshio

doi:10.1016/j.bbrc.2012.08.027

Cited by 14 publications

(22 citation statements)

References 24 publications

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“…HepG2 cells expressing Tet-inducible human CAR, named HepTR/hCAR cells, were established previously (Kanno et al, 2012). In this cell line, Tet acts as a driver of CAR expression mimicking a CAR activator.…”

Section: Resultsmentioning

confidence: 99%

“…The construction of expression plasmids for GAL4/DNAbinding domain (DBD)-fused human CAR (hCAR)/ligand binding domain (LBD) (GAL4/DBD-hCAR/LBD), GAL4/DBD-hCAR/LBD + three amino acid (+3 a.a.), and GAL4/DBD-hPXR/LBD has been reported previously (Kanno and Inouye, 2010;Kanno et al, 2014). Preparation of the hCAR (pcDNA5-hCAR) expression plasmid and penobarbital-responsive enhancer module (PBREM)-driven luciferase reporter plasmid (PBREM-Luc) has also been described previously (Kanno et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…The HepTR/hCAR cell line, in which human CAR was expressed only in the presence of Tet using the T-REx system (Invitrogen, Carlsbad, CA), was previously established by transfection with pcDNA5/TOhCAR and pcDNA6/TR plasmids (Kanno et al, 2012). Stably human PXRoverexpressing HepTR/hCAR (HepTR/hCAR/hPXR) cells were selected by puromycin resistance from HepTR/hCAR cells transfected with the pIRESpuro/hPXR expression plasmid.…”

Section: Methodsmentioning

confidence: 99%

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Differences in Gene Regulation by Dual Ligands of Nuclear Receptors Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) in HepG2 Cells Stably Expressing CAR/PXR

Kanno

Tanuma

Yazawa

et al. 2016

Drug Metabolism and Disposition

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Differences in Gene Regulation by Dual Ligands of Nuclear Receptors Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) in HepG2 Cells Stably Expressing CAR/PXR

Kanno

Tanuma

Yazawa

et al. 2016

Drug Metabolism and Disposition

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“…Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was conducted (40 cycles of 98°C for 5 seconds, 55°C for 20 seconds, and 72°C for 30 seconds) using the dmd.aspetjournals.org THUNDERBIRD SYBR qPCR Mix (Toyobo), according to the manufacturer's protocol, and the 7500 fast system SDS software (Applied Biosystems, Life Technologies, Carlsbad, CA). Specific primers were used to target CYP3A4 (59-CCAAGCTATGCTCTTCACCG-39 and 59-TCAGGCTCCACTTACGGTGC-39) and b-actin (59-TCCTCCTGAGCGCAAGTACTC-39 and 59-CTGCTTGCTGATC-CACATCTG-39) (Kanno et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Nigramide C Is a Natural Agonist of Human Pregnane X Receptor

Kanno¹,

Yatsu²,

Li³

et al. 2014

Drug Metabolism and Disposition

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Pregnane X receptor (PXR) is known as a xenosensor, playing a key role in response to xenochemical stimuli. Activation of PXR enhanced expression of various drug-metabolizing enzymes and transporters such as cytochrome P450 3A4 (CYP3A4). During a screening of a natural compounds library for novel ligands of human xenosensing receptors by the mammalian one-hybrid assay, two cyclohexene-type amide alkaloids were isolated, with nigramide C (NigC) showing the most potent activation of human PXR (hPXR). NigC-mediated hPXR activation was enhanced by overexpression of steroid receptor coactivator 1 (SRC1), peroxisome proliferator-activated receptor g, coactivator 1a, and protein arginine methyltransferase 1. A direct interaction between the ligand-binding domain of hPXR and the receptor interaction domain of SRC1 was observed. NigC induced the expression of endogenous CYP3A4 mRNA and protein in both cultured hepatoma cells and primary hepatocytes. However, in primary hepatocytes, the relative agonist activity of NigC was not as potent as that of rifampicin, probably because of lower metabolic stability of NigC in these cells. In conclusion, NigC was found to be an effective agonist of hPXR. NigC is a useful tool for investigation of hPXR function.

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“…The HepTR/hCAR cell line was established in human hepatoma HepG2 cells; using the T-REx system (Invitrogen, Carlsbad, CA, USA) hCAR was expressed only in the presence of tetracycline (Tet) (Kanno et al, 2012). Human embryonic kidney, HEK293, HepG2, Hep-TR/hCAR and Cos-7 cells were cultured in Dulbecco's modified Eagle's medium (Wako, Osaka, Japan) containing 10% fetal bovine serum and penicillin-streptomycin in a humidified atmosphere containing 5% CO 2 at 37°C.…”

Section: Cell Culturementioning

confidence: 99%

T0901317, a potent LXR agonist, is an inverse agonist of CAR

et al. 2013

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-The basal transcriptional activity of unliganded human constitutive androstane receptor (hCAR) was shown to be repressed by the potent liver X receptor (LXR) agonist, T0901317, in a concentration-dependent manner using a reporter assay in cultured cells. T0901317 also repressed the basal transcriptional activity of both mouse and rat CAR. The certified hCAR agonist, CITCO, partially reversed this repressive effect of T0901317 on hCAR basal activity. Unlike hCAR, a three alanine insertion mutant and the splice variant 2 of hCAR require agonists, such as CITCO, to become transcriptionally active and the CITCO-induced reporter activity was repressed by T0901317. As has been previously shown for the typical hCAR inverse agonist, PK11195, T0901317 blocked the interaction of hCAR with steroid receptor co-activator 1 (SRC1). In contrast, the interaction between hCAR and nuclear receptor corepressor 1 (NCoR1) was promoted by PK11195 and T0901317. Furthermore, the hCAR-mediated basal induction of endogenous cytochrome P450 2B6 (CYP2B6) mRNA was adversely affected by co-treatment with T0901317.

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DP97, a DEAD box DNA/RNA helicase, is a target gene-selective co-regulator of the constitutive androstane receptor

Cited by 14 publications

References 24 publications

Differences in Gene Regulation by Dual Ligands of Nuclear Receptors Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) in HepG2 Cells Stably Expressing CAR/PXR

Differences in Gene Regulation by Dual Ligands of Nuclear Receptors Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) in HepG2 Cells Stably Expressing CAR/PXR

Nigramide C Is a Natural Agonist of Human Pregnane X Receptor

T0901317, a potent LXR agonist, is an inverse agonist of CAR

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