The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion
Jiro Ogura,Yusuke Terada,Takashi Tsujimoto,Takahiro Koizumi,Kaori Kuwayama,Hajime Maruyama,Asuka Fujikawa,Atsushi Takaya,Masaki Kobayashi,Shirou Itagaki,Shirou Itagaki,Natsuko Takahashi,Takeshi Hirano,Takeshi Hirano,Hiroaki Yamaguchi,Ken Iseki +15 more
TL;DR: FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R, and IL-6 is one of main causes the decreases in expressions of these receptors.
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Abstract: Purpose. Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments. Methods. We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts. Results. FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively. Conclusions. FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors.
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References
•Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
318.1K
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Christopher J. Sinal,Masahiro Tohkin,Masaaki Miyata,Jerrold M. Ward,Gilles Lambert,Frank J. Gonzalez +5 more
TL;DR: It is demonstrated that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile Acid sensor.
1.8K
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor
Heidi Rachelle Kast,Bryan Goodwin,Paul T. Tarr,Stacey A. Jones,Andrew M. Anisfeld,Catherine M. Stoltz,Peter Tontonoz,Steve A. Kliewer,Timothy M. Willson,Peter A. Edwards,Peter A. Edwards +10 more
TL;DR: It is demonstrated that MRP2 is regulated by three distinct nuclear receptor signaling pathways that converge on a common response element in the 5′-flanking region of this gene.
980
Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin.
TL;DR: Intestinal P-glycoprotein, which is encoded by the MDR1 gene, plays an important role in the absorption and presystemic elimination of many xenobiotics, and its induction is mediated by a DR4 motif in the upstream enhancer at about −8 kilobase pairs, to which PXR binds.
919
Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity.
Grace L. Guo,Gilles Lambert,Masahiko Negishi,Jerrold M. Ward,H. Bryan Brewer,Steven A. Kliewer,Frank J. Gonzalez,Christopher J. Sinal +7 more
TL;DR: A critical and combined role of FXR and PXR in maintaining not only bile acid but also cholesterol and lipid homeostasis in vivo is demonstrated, suggesting that they serve as redundant but distinct layers of defense to prevent overt hepatic damage by bile acids during cholestasis.
319