Reference - Detail
| RRC ID | 44049 |
|---|---|
| Author | Zhou T, Cong S, Sun S, Sun H, Zou R, Wang S, Wang C, Jiao J, Goto K, Nawata H, Yanase T, Zhao Y. |
| Title | Identification of endocrine disrupting chemicals activating SXR-mediated transactivation of CYP3A and CYP7A1. |
| Journal | Mol Cell Endocrinol |
| Abstract |
Endocrine disrupting chemicals (EDCs) have emerged as a major public health issue because of their potentially disruptive effects on physiological hormonal actions. SXR (steroid xenobiotic receptor), also known as NR1I2, regulates CYP3A expression in response to exogenous chemicals, such as EDCs, after binding to SXRE (SXR response element). In our study, luciferase assay showed that 14 out of 55 EDCs could enhance SXR-mediated rat or human CYP3A gene transcription nearly evenly, and could also activate rat CYP7A1 gene transcription by cross-interaction of SXR and LXRE (LXRα response element). SXR diffused in the nucleus without ligand, whereas intranuclear foci of liganded SXR were produced. Furthermore, endogenous mRNA expression of CYP3A4 gene was enhanced by the 14 positive EDCs. Our results suggested a probable mechanism of EDCs disrupting the steroid or xenobiotic metabolism homeostasis via SXR. |
| Volume | 365(1) |
| Pages | 36-43 |
| Published | 2013-1-5 |
| DOI | 10.1016/j.mce.2012.09.001 |
| PII | S0303-7207(12)00418-2 |
| PMID | 22975079 |
| MeSH | Animals Cell Line Chlorocebus aethiops Cholesterol 7-alpha-Hydroxylase / biosynthesis* Cholesterol 7-alpha-Hydroxylase / genetics Cytochrome P-450 CYP3A / biosynthesis* Cytochrome P-450 CYP3A / genetics Endocrine Disruptors / pharmacology* Endocrine Disruptors / toxicity Genes, Reporter / drug effects Hep G2 Cells Humans Kidney / cytology Kidney / drug effects* Kidney / enzymology Kidney / metabolism Liver / drug effects* Liver / enzymology Liver / metabolism Liver X Receptors Membrane Proteins / biosynthesis Membrane Proteins / genetics Orphan Nuclear Receptors / agonists Orphan Nuclear Receptors / chemistry Orphan Nuclear Receptors / genetics Orphan Nuclear Receptors / metabolism Pregnane X Receptor Promoter Regions, Genetic / drug effects Protein Transport / drug effects Rats Receptors, Steroid / agonists* Receptors, Steroid / chemistry Receptors, Steroid / genetics Receptors, Steroid / metabolism Recombinant Proteins / agonists Recombinant Proteins / genetics Recombinant Proteins / metabolism Response Elements / drug effects Transcriptional Activation / drug effects* |
| IF | 3.871 |
| Times Cited | 5 |
| WOS Category | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | CV-1(RCB0160) Hep G2 |