Iron depletion induces hepatic secretion of biliary lipids and glutathione in rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F17%3A10363518" target="_blank" >RIV/00216208:11150/17:10363518 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/17:10363518 RIV/00216208:11110/17:10363518 RIV/00064165:_____/17:10363518

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S1388198117301889" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1388198117301889</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbalip.2017.09.003" target="_blank" >10.1016/j.bbalip.2017.09.003</a>

Result language

angličtina

Original language name

Iron depletion induces hepatic secretion of biliary lipids and glutathione in rats

Original language description

Iron depletion (ID) has been shown to induce the liver expression of Cyp7a1, the rate-limiting enzyme initiating conversion of cholesterol to bile acids (BA), although the effect on bile acids metabolism and bile production is unknown. Therefore, we investigated changes in bile secretion and BA synthesis during diet-induced iron depletion (ID) in rats. ID increased bile flow along with augmented biliary excretion of bile acids, glutathione, cholesterol and phospholipids. Accordingly, we found transcriptional upregulation of the Cyp7a1, Cyp8b1, and Cyp27a1 BA synthetic enzymes, as well as induction of the Abcg5/8 cholesterol transporters in ID rat livers. In contrast, intravenous infusion of H-3-taurocholate failed to elicit any difference in biliary secretion of this compound in the ID rats. This corresponded with unchanged expression of canalicular rate-limiting transporters for BA as well as glutathione. We also observed that ID substantially changed the spectrum of BA in bile and decreased plasma concentrations of BA and cholesterol. Experiments with differentiated human hepatic flepaRG cells confirmed human CYP7A1 orthologue upregulation resulting from reduced iron concentrations. Results employing a luciferase reporter gene assay suggest that the transcriptional activation of the CYP7A1 promoter under ID conditions works independent of farnesoid X (FXR), pregnane X (PXR) and liver X (LXRalpha) receptors activation. It can be concluded that this study characterizes the molecular mechanisms of modified bile production as well as cholesterol as along with BA homeostasis during ID. We propose complex upregulation of BA synthesis, and biliary cholesterol secretion as the key factors affected by ID.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GA17-06841S" target="_blank" >GA17-06841S: Dynamics of nuclear receptor-mediated gene regulation:implement for the understanding of detoxification functions and optimization of therapy</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

ISSN

1388-1981

e-ISSN

—

Volume of the periodical

1862

Issue of the periodical within the volume

12

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

1469-1480

UT code for WoS article

000414815300001

EID of the result in the Scopus database

2-s2.0-85029495423