ArticleArchives of toxicology2017
Role of AMP-activated protein kinase α1 in 17α-ethinylestradiol-induced cholestasis in rats.
Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- LncRNA H19 as a key regulator in biliary atresia: insights into pathogenesis and potential therapeutic targets.Annals of medicine · 2026Review
- Integrating deep learning and molecular dynamics simulations for FXR antagonist discovery.Molecular diversity · 2025Article
- Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER α degradation.Cell biology and toxicology · 2023Article
- Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes.Journal of physiology and biochemistry · 2023Review
- Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure.World journal of gastroenterology · 2022Article
- The AMPK pathway in fatty liver disease.Frontiers in physiology · 2022Review
- Development of an adverse outcome pathway for intrahepatic cholestasis of pregnancy.Current research in toxicology · 2022Article
- Paeoniflorin alleviates 17α-ethinylestradiol-induced cholestasisFrontiers in pharmacology · 2022Article
- The Aged Intestine: Performance and Rejuvenation.Aging and disease · 2021Review
- SEW2871 attenuates ANIT-induced hepatotoxicity by protecting liver barrier function via sphingosine 1-phosphate receptor-1-mediated AMPK signaling pathway.Cell biology and toxicology · 2021Article
- Kinsenoside Alleviates 17α-Ethinylestradiol-Induced Cholestatic Liver Injury in Rats by Inhibiting Inflammatory Responses and Regulating FXR-Mediated Bile Acid Homeostasis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation.Frontiers in pharmacology · 2021Article
- The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives.Frontiers in pharmacology · 2021Review
- Article
- Population Scale Retrospective Analysis Reveals Potential Risk of Cholestasis in Pregnant Women Taking Omeprazole, Lansoprazole, and Amoxicillin.Interdisciplinary sciences, computational life sciences · 2019Article
- Baicalin Protects Against 17α-Ethinylestradiol-Induced CholestasisFrontiers in pharmacology · 2019Article
- Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans.Hepatology (Baltimore, Md.) · 2018Article
- The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice.Hepatology (Baltimore, Md.) · 2017Article
- Tea and coffee consumption in relation to DNA methylation in four European cohorts.Human molecular genetics · 2017Article
- Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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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.