The Role of the Sodium-taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) in Related Liver Disease

2019 ◽  
Vol 20 (5) ◽  
pp. 377-389 ◽  
Author(s):  
Xiaoyang Lu ◽  
Lin Liu ◽  
Wenya Shan ◽  
Limin Kong ◽  
Na Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Structure Function ◽  
Bile Salt ◽  
Drug Targets ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Bile Salt Export Pump ◽  
Bile Acid Transporters ◽  
Function Relationship ◽  
Related Liver Disease

Background:Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease.Methods:We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP.Results:This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases.Conclusion:NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.

Effect of intestinal resection on bile salt absorption in dogs

1965 ◽  
Vol 208 (2) ◽  
pp. 363-369 ◽  
Author(s):  
M. R. Playoust ◽  
Leon Lack ◽  
I. M. Weiner
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Intestinal Resection ◽  
High Fat ◽  
Salt Absorption ◽  
Complete Failure ◽  
Fat Meal

The efficiency of intestinal absorption of bile salts was evaluated by studying the rate of disappearance of radioactivity from the bile of dogs after the intravenous administration of sodium taurocholate-24-C14. Bile was sampled through an indwelling tube in the gall bladder. One day after a high-fat meal normal dogs retained 48% of the radioactivity; dogs with resection of the jejunum retained 48%, whereas those with resection of the ileum retained only 3% in the bile. This is consistent with previous observations that the ileum is the site of bile salt absorption in vitro and in anesthetized animals. Animals with resection of the ileum exhibited significant steatorrhea; however, three-fourths of the ingested fat was absorbed in spite of almost complete failure to absorb bile salts. This indicates that fat and bile salts are not normally absorbed together. Elimination of enterohepatic circulation of bile salts by resection of the ileum contributes to the observed steatorrhea.

Bile salt export pump is highly conserved during vertebrate evolution and its expression is inhibited by PFIC type II mutations

2001 ◽  
Vol 281 (2) ◽  
pp. G316-G322 ◽  
Author(s):  
Shi-Ying Cai ◽  
Lin Wang ◽  
Nazzareno Ballatori ◽  
James L. Boyer
Keyword(s):  
Bile Salt ◽  
Bile Secretion ◽  
Sf9 Cells ◽  
Bile Salt Export Pump ◽  
Raja Erinacea ◽  
Mutant Proteins ◽  
Liver Cdna Library ◽  
Function Relationship ◽  
Dependent Transport ◽  
Relationship Of

Bile secretion is a fundamental function of the liver of all vertebrates and is generated by ATP-dependent transport proteins at the canalicular membrane of hepatocytes, particularly by the bile salt export pump BSEP. To determine the evolutionary origin and structure-function relationship of this transport mechanism, a liver cDNA library from the marine skate Raja erinacea, a 200 million-year-old vertebrate, was screened for BSEP orthologues. A full-length clone was isolated that encodes for 1,348 amino acids and shares 68.5% identity to human BSEP. Northern blot analysis revealed a 5-kb transcript only in skate liver. Expression of skate Bsep in Sf9 cells demonstrated a sixfold stimulation of ATP-dependent taurocholate transport compared with controls, with a Michaelis-Menten constant of 15 μM, which is comparable to rat Bsep. Sequences at the site of published mutations in human BSEP are also conserved in skate Bsep. When two of these mutations were introduced into the skate Bsep cDNA, this resulted in defective expression of the mutant proteins in Sf9 cells. These studies demonstrate that Bsep is a liver-specific ATP-dependent export pump that is highly conserved throughout evolution and provide insights into critical determinants for the function of this transporter in higher vertebrates.

scholarly journals Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs

2012 ◽  
Vol 302 (2) ◽  
pp. G218-G224 ◽  
Author(s):  
Ajay Kumar Jain ◽  
Barbara Stoll ◽  
Douglas G. Burrin ◽  
Jens J. Holst ◽  
David D. Moore
Keyword(s):  
Liver Disease ◽  
Parenteral Nutrition ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Regulatory Peptides ◽  
Serum Markers ◽  
Direct Bilirubin ◽  
Neonatal Pigs ◽  
Mucosal Growth ◽  
Related Liver Disease

Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly described metabolic hormone fibroblast growth factor-19 (FGF19) and also glucagon-like peptides-1 and -2 (GLP-1 and GLP-2). We tested the effects of restoring bile acids by treating a neonatal piglet PNALD model with chenodeoxycholic acid (CDCA). Neonatal pigs received enteral feeding (EN), TPN, or TPN + CDCA for 14 days, and responses were assessed by serum markers, histology, and levels of key regulatory peptides. Cholestasis and steatosis were demonstrated in the TPN group relative to EN controls by elevated levels of serum total and direct bilirubin and also bile acids and liver triglyceride (TG) content. CDCA treatment improved direct bilirubin levels by almost fourfold compared with the TPN group and also normalized serum bile acids and liver TG. FGF19, GLP-1, and GLP-2 were decreased in plasma of the TPN group compared with the EN group but were all induced by CDCA treatment. Intestinal mucosal growth marked by weight and villus/crypt ratio was significantly reduced in the TPN group compared with the EN group, and CDCA treatment increased both parameters. These results suggest that decreased circulating FGF19 during TPN may contribute to PNALD. Moreover, we show that enteral CDCA not only resolves PNALD but acts as a potent intestinal trophic agent and secretagogue for GLP-2.

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