Navigation Links
Farnesoid X receptor regulates cystathionase
Date:5/13/2009

The expression and activity of Cystathionase is reduced in rodent models of liver injury, leading to hyper-homocysteinemia and impaired generation of hydrogen sulphide, two factors that contribute to endothelial dysfunction and increased intrahepatic resistance.

In the present study the analysis of the human Cystathionase gene promoter demonstrates the presence of an inverted repeat sequence. Administration of an FXR ligand to carbon tetrachloride treated mice protected against down-regulation of Cystathionase expression, increased hydrogen sulphide generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused livers.

A research article to be published on May 7, 2009 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Barbara Renga and her colleagues in the University of Perugia, Italy used luciferase transfection assay, Electrophoretic Mobility Shift Assay (EMSA), Chromatin Immunoprecipitation Assay and Real-Time PCR to confirm the role of FXR in the regulation of CSE transcription.

The molecular mechanism of the CSE activation by FXR was revealed by identifying a sequence in the 5' flanking region of CSE gene containing a potential IR1 binding site. Co-transfection of HepG2 cells with luciferase reporter vector containing four copies of this putative IR1 resulted in transactivation of the CSE promoter in presence of an FXR ligand, while the mutation of the IR1 binding site abrogates this response. The functionality of this IR1 site was also confirmed by EMSA and CHIP assay.

In the normal liver the CSE expression was significantly increased when mice were fed a chow diet supplemented with 5 mg/kg body weight of 6E-CDCA while the FXR ligand failed to up-regulate CSE mRNA expression in FXR knock-out mice.

Contraction of presinusoidal myofibroblasts has relevance in regulating intrahepatic resistance and short term administration of 6E-CDCA regulates CSE expression in normal mice, therefore the authors have investigated whether acute administration of an FXR ligand effectively modulates CSE expression in CCl4 treated mice. The author demonstrated that CSE liver expression was down-regulated in an animal model of liver damage induced by CCl4 and that treatment with 6E-CDCA resulted in a robust induction of CSE expression only in FXR +/+ mice

The reduction of CSE expression in the cirrhotic liver contributes to the development of increased intrahepatic resistance and portal hypertension. The authors therefore investigated whether in vivo administration of an FXR ligand modulates hepatic resistance in cirrhotic rats.

In conclusion, they have shown that CSE is an FXR-regulated gene. By linking the deficiency of CSE to the FXR activity the present study provides a new molecular explanation to the pathophysiology of portal hypertension. It also proposes the concept that FXR agonists might correct for the altered generation of endogenous hepatic vasodilators that takes place in chronic liver diseases.


'/>"/>

Contact: Lin Tian
wjg@wjgnet.com
86-105-908-0039
World Journal of Gastroenterology
Source:Eurekalert

Related medicine news :

1. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
2. Low level of neuronal receptor linked to mild cognitive impairment and Alzheimers disease
3. Pathway Diagnostics Announces Commercial Availability of SensiTrop(TM) HIV Co-receptor Tropism Assay
4. Pharmacopeia Acquires Selective Androgen Receptor Modulator (SARM) Program from Bristol-Myers Squibb
5. Food restriction increases dopamine receptor levels in obese rats
6. Quest Diagnostics Licenses Technology Underlying SensiTrop(TM) HIV Co-Receptor Tropism Test from Pathway Diagnostics
7. Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
8. Exelixis to Receive Milestone Payment From Bristol-Myers Squibb for Achievement of Liver X Receptor Agonist Development Milestone
9. Receptor protein appears to be key in breakdown of kidney filtration
10. Cell-death receptor links cancer susceptibility and inflammation
11. Food peptides activate bitter taste receptors
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... ... February 09, 2016 , ... Shark Finds and Kevin Harrington, and the Product ... GRIP-DRY. , GRIP-DRY is a newly patented product that has solved some of the basic ... wet and early morning dew or right after a rain shower, might understand the struggle ...
(Date:2/8/2016)... ... February 08, 2016 , ... CURE Media Group , the ... the Multiple Myeloma Heroes Awards event , which will annually honor individuals making ... patients with MM. The MM Heroes Awards nomination process is officially open ...
(Date:2/8/2016)... PA (PRWEB) , ... February 08, 2016 , ... ... expanded authorization with BASF Human Nutrition into the Food & Beverage ... BSI has been BASF’s channel partner throughout Canada and USA geographies east of ...
(Date:2/8/2016)... ... February 08, 2016 , ... Stephanie Hebert Insurance Agency, serving ... a new charity campaign. As part of their ongoing community involvement program, funds ... belief that children deserve a voice, and in the spirit of neighbors helping ...
(Date:2/8/2016)... ... ... who has struggled to quit smoking, a man who has struggled with hair loss – ... his problems – and he did. Now Nabat, a serial entrepreneur featured as the October ... to the world and better people's lives. His own experience with nicotine addiction led to ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)... , Feb. 9, 2016  Johnson & Johnson (NYSE: ... Markets Global Healthcare Conference on Tuesday, Feb. 23, at ... Dominic Caruso , Vice President, Finance & Chief Financial ... will represent the Company in a session scheduled at ... --> www.investor.jnj.com . --> This ...
(Date:2/9/2016)...  The Parenteral Drug Association, Inc. (PDA), the ... sterile drug products, today announced the publication of ... With link to Comparison Spreadsheet. The document ... FDA, the EU, the Pharmaceutical Inspection Convention/Scheme and ... --> PDA,s Global Sterile Task ...
(Date:2/8/2016)... 2016 Aesthetic Devices - Medical Devices Pipeline ... report, "Aesthetic Devices - Medical Devices Pipeline Assessment, 2015" ... stage. This report is prepared using ... by GlobalData,s team of industry experts. *Note: Certain ... based on the availability and relevance of data in ...
Breaking Medicine Technology: