A systems-level analysis of bile acids effects on rat colon epithelial cells

2021 ◽  
Author(s):  
Jonathan Yde ◽  
Qi Wu ◽  
Johan Borg ◽  
Robert A. Fenton ◽  
Hanne Bjerregaard Moeller
Keyword(s):  
Mass Spectrometry ◽  
Bile Acid ◽  
Epithelial Cells ◽  
Bile Acids ◽  
Rna Sequencing ◽  
Urine Volume ◽  
Rat Colon ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
Underlying Mechanisms

Bile acid diarrhoea is a chronic condition caused by increased delivery of bile acids to the colon. The underlying mechanisms remain to be elucidated. To investigate genes involved in bile acid diarrhoea, systems-level analyses were employed on a rat bile acid diarrhoea model. Twelve male Wistar Munich rats, housed in metabolic cages, were fed either control or bile acid-mixed (1% w/w) diets for ten days. Food intake, water intake, urine volume, bodyweight and faecal output were monitored daily. After euthanasia, colonic epithelial cells were isolated using calcium-chelation and processed for systems-level analyses, i.e. RNA-sequencing transcriptomics and mass spectrometry proteomics. Bile acid-fed rats suffered diarrhoea, indicated by increased drinking, faeces weight and faecal water content compared with control rats. Urine output was unchanged. With bile acid-feeding, RNA-sequencing revealed 204 increased and 401 decreased mRNAs; mass spectrometry 183 increased and 111 decreased proteins. Among the altered genes were genes associated with electrolyte and water transport (including Slc12a7, Clca4 and Aqp3) and genes associated with bile acid transport (Slc2b1, Abcg2, Slc51a, Slc51b and Fabps). Correlation analysis showed a significant positive correlation (Pearson's r=0.28) between changes in mRNA-expression and changes in protein-expression. However, caution must be exercised in making a direct correlation between experimentally determined transcriptomes and proteomes. Genes associated with bile acid transport responded to bile acid-feeding, suggesting that colonic bile acid transport also occur by regulated protein facilitated mechanisms in addition to passive diffusion. In summary, the study provides annotated rat colonic epithelial cell transcriptome and proteome with response to bile acid-feeding.

scholarly journals Properties of the canalicular bile acid transport system in rat liver

1987 ◽  
Vol 242 (2) ◽  
pp. 465-469 ◽  
Author(s):  
P J Meier ◽  
A S Meier-Abt ◽  
J L Boyer
Keyword(s):  
Bile Acid ◽  
Substrate Specificity ◽  
Bile Acids ◽  
Rat Liver ◽  
Transport System ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
Canalicular Bile ◽  
Disulphonic Acid ◽  
Bile Acid Carrier

4,4-Di-isothiocyanostilbene-2,2′-disulphonic acid inhibition of taurocholate efflux from canalicular vesicles was used to demonstrate that potential driven and ‘carrier’-mediated canalicular excretion of taurocholate occur via a common, rather than two separate, pathways. This electrogenic canalicular bile acid ‘carrier ’ preferentially transports trihydroxylated and conjugated dihydroxylated bile acids, but not the unphysiological oxo bile acids, and possibly extends its substrate specificity to other amphipathic molecules such as sulphobromophthalein.

FRI-060-Effects of the ileal bile acid transport inhibitor A4250 on pruritus and serum bile acids in patients with biliary atresia: phase 2 study results

2019 ◽  
Vol 70 (1) ◽  
pp. e411 ◽  
Author(s):  
Ulrich Baumann ◽  
Ekkehard Sturm ◽  
Florence Lacaille ◽  
Emmanuel Gonzales ◽  
Henrik Arnell ◽  
...  
Keyword(s):  
Bile Acid ◽  
Biliary Atresia ◽  
Bile Acids ◽  
Phase 2 ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
Serum Bile Acids ◽  
Transport Inhibitor ◽  
Phase 2 Study ◽  
Study Results

I. Hepatocyte transport of bile acids

2003 ◽  
Vol 284 (2) ◽  
pp. G175-G179 ◽  
Author(s):  
Allan W. Wolkoff ◽  
David E. Cohen
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Plasma Membranes ◽  
Enterohepatic Circulation ◽  
Bile Canaliculus ◽  
Transport Proteins ◽  
Acid Transport ◽  
Bile Acid Transport ◽  
The Past ◽  
The Subject

Bile acids are cholesterol derivatives that serve as detergents in bile and the small intestine. Approximately 95% of bile acids secreted by hepatocytes into bile are absorbed from the distal ileum into the portal venous system. Extraction from the portal circulation by the hepatocyte followed by reexcretion into the bile canaliculus completes the enterohepatic circulation of these compounds. Over the past few years, candidate bile acid transport proteins of the sinusoidal and canalicular plasma membranes of the hepatocyte have been identified. The physiology of hepatocyte bile acid transport and its relationship to these transport proteins is the subject of this Themes article.

ATP-dependent bile acid transport across microvillous membrane of human term trophoblast

1995 ◽  
Vol 268 (4) ◽  
pp. G685-G694 ◽  
Author(s):  
J. J. Marin ◽  
P. Bravo ◽  
M. Y. el-Mir ◽  
M. A. Serrano
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Plasma Membranes ◽  
Temperature Sensitive ◽  
Acid Transport ◽  
Human Trophoblast ◽  
Bile Acid Transport ◽  
Carbonyl Cyanide ◽  
Dependent Transport ◽  
Filtration Technique

The main fate for fetal bile acids is to be transferred to the mother by the trophoblast. In this study, ATP-dependent bile acid transport across the maternal- and the fetal-facing plasma membranes (mTPM and fTPM, respectively) of the human trophoblast was investigated. With the use of [14C]glycocholate (GC) and a rapid-filtration technique, GC transport by mTPM and fTPM was measured in the absence or the presence of 3 mM ATP plus an ATP-regenerating system. GC efflux from preloaded mTPM or fTPM vesicles was found to be insensitive to ATP. By contrast, GC uptake by mTPM, but not by fTPM, was significantly increased (approximately threefold) by ATP. This was temperature sensitive and occurred into an osmotically reactive space. Kinetic analysis revealed that GC uptake by mTPM was saturable and fit the Michaelis-Menten equation both in the absence and in the presence of ATP. ATP-dependent transport was not abolished by a protonophore (carbonyl cyanide p-trifluormethoxyphenyl hydrazone) together with 100 mM K+ (in = out) plus a K+ ionophore (valinomycin). It specifically required hydrolyzable ATP, although CTP had a slight stimulatory effect. Neither Na+ nor Cl- (100 mM, in = out) was mandatory. Moreover, 100 mM gradients of either Na+ (in << out) or Cl- (in >> out) had no effect on ATP-dependent GC uptake. This was inhibited by vanadate and bile acid analogues but not by several cholephilic organic anions and a variety of adenosine triphosphatase inhibitors. These results provide strong evidence for the existence of an ATP-dependent transport system for bile acids across the apical membrane of human trophoblast, which may play an important role in the control of the overall fetal-maternal bile acid traffic.

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