Homologue gene of bile acid transporters ntcp, asbt, and ost-alpha in rainbow trout Oncorhynchus mykiss: tissue expression, effect of fasting, and response to bile acid administration

Abstract

Bile acid transporters belonging to the SLC10A protein family, Na+ taurocholate cotransporting polypeptide (NTCP or SLC10A1), apical sodium-dependent bile salt transporter (ASBT or SLC10A2), and organic solute transporter alpha (Ost-alpha) have been known to play critical roles in the enterohepatic circulation of bile acids in mammals. In this study, ntcp, asbt, and ost-alpha-1/-2 cDNA were cloned, their tissue distributions were characterized, and the effects of fasting and bile acid administration on their expression were examined in rainbow trout Oncorhynchus mykiss. The structural characteristics of Ntcp, Asbt, and Ost-alpha were well conserved in trout, and three-dimensional structure analysis showed that Ntcp and Asbt were similar to each other. Tissue distribution analysis revealed that trout asbt was primarily expressed in the hindgut, while ntcp expression occurred in the brain, and ost-alpha-1/-2 was mainly expressed in the liver or ovary. Although asbt and ost-alpha-1 mRNA levels in the gut increased in response to fasting for 4 days, ost-alpha-1 expression in the liver decreased. Similarly, bile acid administration increased asbt and ost-alpha-1 expression levels in the gut, while those of ntcp and ost-alpha-2 in the liver decreased. These results suggested that the genes asbt, ntcp, and ost-alpha are involved in bile acid transport in rainbow trout.

Na+-taurocholate cotransporting polypeptide (NTCP/SLC10A1) ortholog in the marine skateLeucoraja erinaceais not a physiological bile salt transporter

“…Therefore, we propose that neurosteroid conjugates are evolutionarily conserved endogenous substrates for the SLC10A1/Slc10a1 transporter. This speculation is also supported by its tissue distribution in skate and rainbow trout, where it is mainly expressed in the brain and testis (14) (Fig. 2).…”

“…3A). This expression pattern is similar to Slc10a1 in rainbow trout but strikingly different from NTCP/SLC10A1 in humans and mice (10,14,22) (Fig. 3B).…”

“…Very recently, Murashita et al (14) identified an Slc10a1 gene in rainbow trout and found that its expression was most abundant in the brain. However, it is not known whether this protein can transport bile salts.…”

Structure-based Discovery of Potential Inhibitors Targeting Sodium-bile Acid Co-transporter of Carcinogenic Liver Fluke Clonorchis Sinensis

“…After comprehensive evaluation, we applied Swiss-Model for reliable 3D modeling, and thereafter, FG-MD and GalaxyRe ne were used for effective re nement. In fact, Swiss-Model has been a powerful tool for transporter modeling [62,63]. Re ning enhanced the structural quality of the nal model compared to that of the initial model, particularly in terms of ERRAT values, which were increased from 46.0-97.7% (Tables 1 and 2 2 Cov: Sequence coverage, ratio of predicted region relative to whole region 3 Symbol " ": corresponding software was applied.…”

Structure-based discovery of potential inhibitors targeting sodium-bile acid co-transporter of carcinogenic liver fluke Clonorchis sinensis

“…After comprehensive evaluation, we applied Swiss-Model for reliable 3D modeling, and thereafter, FG-MD and GalaxyRe ne were used for effective re nement. In fact, Swiss-Model has been a powerful tool for transporter modeling [63,64]. Re ning enhanced the structural quality of the nal model compared to that of the initial model, particularly in terms of ERRAT values, which were increased from 46.0% to 97.7% (Tables 1 and 2 2 Cov: Sequence coverage, ratio of predicted region relative to whole region 3 Symbol " ": corresponding software was applied.…”