Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes

Benoki, Satoshi; Yoshinari, Kouichi; Chikada, Tsubasa; Imai, Jun; Yamazoe, Yasushi

doi:10.1016/j.abb.2011.10.014

Cited by 21 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In primary human hepatocytes, exposure to certain NR ligands resulted in enhanced ABCG2 mRNA expression, strongly suggesting the regulatory role of the PXR and CAR pathways ( Jigorel et al, 2006). In a following study, a CAR/RXRα-binding motif in the distal promoter of ABCG2 was identified and, interestingly, ABCG2 transactivation through this motif was found to occur via CAR but not PXR binding (Benoki, Yoshinari, Chikada, Imai, & Yamazoe, 2012). In contrast, it has been reported that LXR agonists do not activate the transcription of ABCG2 either in the …”

Section: P0305mentioning

confidence: 85%

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

Hegedüs

Telbisz

Hegedüs

et al. 2015

Advances in Cancer Research

View full text Add to dashboard Cite

Section: P0305mentioning

confidence: 85%

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

Hegedüs

Telbisz

Hegedüs

et al. 2015

Advances in Cancer Research

View full text Add to dashboard Cite

“…As a result, the elimination of hydrolytic metabolites of drugs may vary depending on the relative changes of the activities of particular transporters [30]. Interestingly, phenobarbital has been shown to induce many transporters as well [31]. …”

Section: Discussionmentioning

confidence: 99%

Age-related inducibility of carboxylesterases by the antiepileptic agent phenobarbital and implications in drug metabolism and lipid accumulation

Xiao

Chen

Yang

et al. 2012

Biochemical Pharmacology

View full text Add to dashboard Cite

Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids.

show abstract

“…Studies of the BCRP promoter reveal estrogen receptor-binding elements, PPARγ binding sites, and aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR) response elements (58). …”

Section: Cellular and Molecular Determinants Of Bile Formationmentioning

confidence: 99%

Bile Formation and Secretion

Boyer

2013

Comprehensive Physiology

681

602

View full text Add to dashboard Cite

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions.

show abstract

Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes

Cited by 21 publications

References 35 publications

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

Age-related inducibility of carboxylesterases by the antiepileptic agent phenobarbital and implications in drug metabolism and lipid accumulation

Bile Formation and Secretion

Contact Info

Product

Resources

About