ArticleMolecular pharmacology2009
The aldo-keto reductase Akr1b7 gene is a common transcriptional target of xenobiotic receptors pregnane X receptor and constitutive androstane receptor.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Bile acid regulation of xenobiotic nuclear receptors on the expressions of orosomucoids in the liver.American journal of physiology. Endocrinology and metabolism · 2025Article
- The Pregnane-X receptor regulates steroid synthesis in mouse Leydig cells.Frontiers in endocrinology · 2024Article
- Flexible and multifaceted: the plasticity of renin-expressing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Widespread Dysregulation of Long Noncoding Genes Associated With Fatty Acid Metabolism, Cell Division, and Immune Response Gene Networks in Xenobiotic-exposed Rat Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- 3β, 6β-dichloro-5-hydroxy-5α-cholestane facilitates neuronal development through modulating TrkA signaling regulated proteins in primary hippocampal neuron.Scientific reports · 2019Article
- Next Generation Sequencing for Long Non-coding RNAs Profile for CD4Frontiers in genetics · 2019Article
- Chemical Activation of the Constitutive Androstane Receptor Leads to Activation of Oxidant-Induced Nrf2.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Role of the pregnane X receptor in binge ethanol-induced steatosis and hepatotoxicity.The Journal of pharmacology and experimental therapeutics · 2018Article
- Article
- Juxtaglomerular Cell Phenotypic Plasticity.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2017Review
- Identification and functional characterization of four novel aldo/keto reductases in Anabaena sp. PCC 7120 by integrating wet lab with in silico approaches.Functional & integrative genomics · 2017Article
- RNA-Seq reveals common and unique PXR- and CAR-target gene signatures in the mouse liver transcriptome.Biochimica et biophysica acta · 2016Article
- Toxicogenomic assessment of liver responses following subchronic exposure to furan in Fischer F344 rats.Archives of toxicology · 2016Article
- Irisin Is Regulated by CAR in Liver and Is a Mediator of Hepatic Glucose and Lipid Metabolism.Molecular endocrinology (Baltimore, Md.) · 2016Article
- A targeted in vivo SILAC approach for quantification of drug metabolism enzymes: regulation by the constitutive androstane receptor.Journal of proteome research · 2014Article
- The human constitutive androstane receptor promotes the differentiation and maturation of hepatic-like cells.Developmental biology · 2013Article
- Tissue distribution, ontogeny, and chemical induction of aldo-keto reductases in mice.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.Diabetes · 2012Article
- Role of CAR and PXR in xenobiotic sensing and metabolism.Expert opinion on drug metabolism & toxicology · 2012Review
- Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters.Biochemical pharmacology · 2012Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Aldo-keto reductase (AKR) family 1, member 7 (AKR1B7), a member of the AKR superfamily, has been suggested to play an important role in the detoxification of lipid peroxidation by-products. The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are xenosensors postulated to alleviate xeno- and endobiotic chemical insults. In this study, we show that the mouse Akr1b7 is a shared transcriptional target of PXR and CAR in the liver and intestine. Treatment of wild-type mice with the PXR agonist pregnenolone-16alpha-carbonitrile (PCN) activated Akr1b7 gene expression, whereas the effect was abrogated in PXR(-/-) mice. Similarly, the activation of Akr1b7 gene expression by the CAR agonist 1,4-bis[2-(3,5-dichlorpyridyloxyl)]-benzene, seen in wild-type mice, was abolished in CAR(-/-) mice. The promoter of Akr1b7 gene was activated by PXR and CAR, and this activation was achieved through the binding of PXR-retinoid X receptor (RXR) or CAR-RXR heterodimers to direct repeat-4 type nuclear receptor-binding sites found in the Akr1b7 gene promoter. At the functional level, treatment with PCN in wild-type mice, but not PXR(-/-) mice, led to a decreased intestinal accumulation of malondialdehyde, a biomarker of lipid peroxidation. The regulation of Akr1b7 by PXR was independent of the liver X receptor (LXR), another nuclear receptor known to regulate this AKR isoform. Because a major function of Akr1b7 is to detoxify lipid peroxidation, the PXR-, CAR-, and LXR-controlled regulatory network of Akr1b7 may have contributed to alleviate toxicity associated with lipid peroxidation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.