ArticleLiver international : official journal of the International Association for the Study of the Liver2015
The organic solute transporters alpha and beta are induced by hypoxia in human hepatocytes.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells.Pediatric research · 2025Article
- Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside.Pharmacology & therapeutics · 2020Review
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment.World journal of stem cells · 2019Article
- Bile Acid Transporters Are Expressed and Heterogeneously Distributed in Rat Bile Ducts.Gut and liver · 2019Article
- Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Novel in Vitro Method Reveals Drugs That Inhibit Organic Solute Transporter Alpha/Beta (OSTα/β).Molecular pharmaceutics · 2019Article
- Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Article
- Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- SIRT3 a Major Player in Attenuation of Hepatic Ischemia-Reperfusion Injury by Reducing ROS via Its Downstream Mediators: SOD2, CYP-D, and HIF-1Oxidative medicine and cellular longevity · 2018Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe organic solute transporters alpha and beta (OSTα-OSTβ) form a heterodimeric transporter located at the basolateral membrane of intestinal epithelial cells and hepatocytes. Liver injury caused by ischaemia-reperfusion, cancer, inflammation or cholestasis can induce a state of hypoxia in hepatocytes. Here, we studied the effect of hypoxia on the expression of OSTα-OSTβ.
methodsOSTα-OSTβ expression was measured in Huh7 cells and primary human hepatocytes (PHH) exposed to chenodeoxycholic acid (CDCA), hypoxia or both. OSTα-OSTβ promoter activity was analysed in luciferase reporter gene assays. Binding of hypoxia-inducible factor-1 alpha (HIF-1α) to the OSTα-OSTβ gene promoters was studied in electrophoretic mobility shift assays (EMSA).
resultsExpression of OSTα and OSTβ increased in PHH under conditions of hypoxia. Exposure of Huh7 cells or PHH to CDCA (50 μM) enhanced the effect of hypoxia on OSTα mRNA levels. In luciferase assays and EMSA, the inducing effect of low oxygen could be assigned to HIF-1α, which binds to hypoxia responsive elements (HRE) in the OSTα and OSTβ gene promoters. Site-directed mutagenesis of either the predicted HRE or the bile acid responsive FXR binding site abolished inducibility of the OSTα promoter, indicating that both elements need to be intact for induction by hypoxia and CDCA. In a rat model of chronic renal failure, the known increase in hepatic OSTα expression was associated with an increase in HIF-1α protein levels.
conclusionOSTα-OSTβ expression is induced by hypoxia. FXR and HIF-1α bind in close proximity to the OSTα gene promoter and produce synergistic effects on OSTα expression.
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