| http://purl.uniprot.org/citations/27090119 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27090119 | http://www.w3.org/2000/01/rdf-schema#comment | "Estrogen-induced cholestasis occurs in many women who are susceptible due to pregnancy or hormone replacement therapy for postmenopausal syndrome. 17α-Ethinylestradiol (EE), as a synthetic estrogen, has been widely used to study the underlying mechanisms of estrogen-induced cholestasis. Recent studies have also reported that liver kinase B1 (LKB1)-mediated activation of AMP-activated protein kinase (AMPK) plays a critical role in the regulation of canalicular network formation. However, the role of AMPK in EE-induced cholestasis remains to be determined. In this study, the effects of EE (1-100 µM) on AMPK activation and the expression of farnesoid X receptor (FXR) and hepatic bile acid transporters were examined in in vitro using 3D-cultured rat primary hepatocytes and in in vivo using rat cholestasis models. We also used specific chemical agonist and antagonist of AMPK, AMPK subunit-specific antibodies and lentiviral shRNAs for AMPKα1 and AMPKα2 to delineate the role of AMPK in EE-induced cholestasis and potential cellular mechanisms. We found that EE-induced phosphorylation of AMPKα1 via extracellular signal-regulated kinases-LKB1-mediated signaling pathways and subsequent nuclear translocation accounted for the down-regulation of FXR and bile acid transporters and disruption of bile acid homeostasis. Inhibition of AMPK activation using an AMPK antagonist Compound C (2 µM) or down-regulation of AMPKα1 using gene-specific shRNA attenuated EE-induced cholestasis both in in vitro and in in vivo. In conclusion, these results revealed that activation of cAMP-ERK-LKB1-AMPKα1 signaling pathway plays a critical role in EE-mediated dysregulation of the expression of FXR and bile acid transporters. AMPKα1 may represent an important therapeutic target for estrogen-induced cholestasis."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00204-016-1697-8"xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Liu R."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Luo L."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Sun L."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Zhou H."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Yu L."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Jiang Z."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/author | "Hylemon P.B."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/name | "Arch Toxicol"xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/pages | "481-494"xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/title | "Role of AMP-activated protein kinase alpha1 in 17alpha-ethinylestradiol-induced cholestasis in rats."xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://purl.uniprot.org/core/volume | "91"xsd:string |
| http://purl.uniprot.org/citations/27090119 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27090119 |
| http://purl.uniprot.org/citations/27090119 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27090119 |
| http://purl.uniprot.org/uniprot/P54645#attribution-994CF0A961E5C5FD3A0242B95411CD70 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27090119 |
| http://purl.uniprot.org/uniprot/O70127#attribution-994CF0A961E5C5FD3A0242B95411CD70 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27090119 |
| http://purl.uniprot.org/uniprot/Q63120#attribution-994CF0A961E5C5FD3A0242B95411CD70 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27090119 |
| http://purl.uniprot.org/uniprot/P26435#attribution-994CF0A961E5C5FD3A0242B95411CD70 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/27090119 |