Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3

Suga, Toshio; Yamaguchi, Hiroaki; Sato, Toshihiro; Maekawa, Masamitsu; Goto, Junichi; Mano, Nariyasu

doi:10.1371/journal.pone.0169719

Cited by 84 publications

(60 citation statements)

References 47 publications

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“…The 14 human GLUT proteins, encoded by the SLC2 gene, have various substrate specificities and are involved in the transport of several hexoses in addition to myoinositol . GLUT proteins in the digestive system serve as important mediators in maintaining normal functions, including the absorption of nutrients and ions, excretion of bile acids, and metabolism of toxins . Dysregulation of the SLC2 gene is likely to be associated with carcinogenesis, tumor progression, metastasis, and chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

“…39 GLUT proteins in the digestive system serve as important mediators in maintaining normal functions, including the absorption of nutrients and ions, excretion of bile acids, and metabolism of toxins. [40][41][42] Dysregulation of the SLC2 gene is likely to be associated with carcinogenesis, tumor progression, metastasis, and chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

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Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk

et al. 2019

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Pancreatic cancer (PanC) is one of the most lethal solid malignancies, and metastatic PanC is often present at the time of diagnosis. Although several high‐ and low‐penetrance genes have been implicated in PanC, their roles in carcinogenesis remain only partially elucidated. Because the nuclear factor erythroid2‐related factor2 (NRF2) signaling pathway is involved in human cancers, we hypothesize that genetic variants in NRF2 pathway genes are associated with PanC risk. To test this hypothesis, we assessed associations between 31 583 common single nucleotide polymorphisms (SNP) in 164 NRF2‐related genes and PanC risk using three published genome‐wide association study (GWAS) datasets, which included 8474 cases and 6944 controls of European descent. We also carried out expression quantitative trait loci (eQTL) analysis to assess the genotype‐phenotype correlation of the identified significant SNP using publicly available data in the 1000 Genomes Project. We found that three novel SNP (ie, rs3124761, rs17458086 and rs1630747) were significantly associated with PanC risk ( P = 5.17 × 10 −7 , 5.61 × 10 −4 and 5.52 × 10 −4 , respectively). Combined analysis using the number of unfavorable genotypes (NUG) of these three SNP suggested that carriers of two to three NUG had an increased risk of PanC ( P < 0.0001), compared with those carrying zero to one NUG. Furthermore, eQTL analysis showed that both rs3124761 T and rs17458086 C alleles were associated with increased mRNA expression levels of SLC2A6 and SLC2A13 , respectively ( P < 0.05). In conclusion, genetic variants in NRF2 pathway genes could play a role in susceptibility to PanC, and further functional exploration of the underlying molecular mechanisms is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk

et al. 2019

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“…Furthermore, OATP1A2 works effectively in the sodium‐depleted buffer. However, OATP1B1 and OATP1B3 are sodium‐dependent (Suga et al, ).…”

Section: Discussionmentioning

confidence: 99%

Transport mechanism of ursodeoxycholic acid in human placental BeWo cells

Xia

Dong

Zhao

et al. 2018

Biopharm & Drug Disp

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Ursodeoxycholic acid (UDCA) is a first-line drug to treat intrahepatic cholestasis of pregnancy (ICP). However, its effects on the fetus are not clearly known. To better guide its clinical use, we aimed to study the mechanism underlying the placental transport of UDCA. The uptake and efflux of UDCA across placental apical membranes were studied using BeWo cells; effects of different exposure durations, UDCA concentrations, temperatures, and inhibitors of transporters were studied. A transwell assay was performed, and UDCA concentration in both fetal and maternal sides was measured using LC-MS/MS. Higher unidirectional transport of UDCA was observed in the basolateral-to-apical direction than in the apical-to-basolateral direction. Ko143 and verapamil, which are typical inhibitors of efflux transporters, significantly increased UDCA transport from different directions. UDCA uptake from the apical membrane of BeWo cells was time-dependent, but sodium-independent. It was inhibited by inhibitors of energy metabolism and of organic anion transporters, indicating an active transport mechanism. UDCA uptake from the apical membranes of BeWo cells could be mediated by organic anion-transporting polypeptides, whereas its efflux could be mediated by breast cancer resistance protein and multidrug resistant protein 3. The results of the present study may provide a basis for UDCA use in pregnancy.

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“…SLCO1B3 shows obvious gene polymorphism (de Morree et al, 2016). Notably, 334T>G and 699G>A haplotypes can markedly affect the transport activity of OATP1B3 (Bedewy and ElMaghraby, 2013;Suga et al, 2017). Therefore, they can mediate drug-drug interaction and result in individual difference in clinical medication.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, structure, substrate/inhibitor, pharmacogenetics, and the drug-drug interaction mediated by OATP1B1 are the focuses of previous clinical studies (Wang et al, 2013). It is found recently that OATP1B3 can transport the common substrate of OATP1B1 (Suga et al, 2017). Besides, it can also transport multiple substances that do not act with OATP1B1, such as digoxin, paclitaxel and docetaxel.…”

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confidence: 99%

Association between SLCO1B3 gene polymorphism and prostate cancer risk: A meta-analytic study

Shen

Liang

et al. 2018

Bangladesh J Pharmacol

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<p class="Abstract">The aim of this meta-analysis was to assess the association between SLCO1B3 gene polymorphism and prostate cancer risk. PubMed, Embase, Cochrane Library, and Web of Science from inception to September 2017 were searched. Three authors independently selected studies, extracted data and assessed risk of bias. 5 articles published from 2008 to 2013 with 840 patients were included in this meta-analysis and were from Japan, USA and China. The prostate cancer risk of SLCO1B3 (rs4149117, GG) was markedly higher than that of SLCO1B3 (rs4149117, TT/TG, RR= 0.44, 95%CI: 0.39-0.49, p<0.00001), rs4149117 (TT, RR= 0.37, 95%CI: 0.32-0.42, p<0.00001) and rs4149117 (TG, RR= 0.07, 95%CI: 0.05-0.10, p<0.00001). 2 or 5 years risk free symptoms (RFS) of prostate cancer patient with SLCO1B3 (rs4149117, GG) was markedly higher than that of SLCO1B3 (rs4149117, TT/TG) (RR= -0.17, 95% CI: -0.27--0.07, p= 0.001 and RR= -0.08, 95% CI: -0.16-0.00, p= 0.004). However, no evidence showed there existed significant statistical relationship between SLCO1B3 (rs4149117) and 10 years RFS of prostate cancer (RR= -0.07, 95% CI: -0.19-0.06, p= 0.29). These data suggest that SLCO1B3 (rs4149117, GG) enhanced the RFS of prostate cancer.</p>

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Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3

Cited by 84 publications

References 47 publications

Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk

Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk

Transport mechanism of ursodeoxycholic acid in human placental BeWo cells

Association between SLCO1B3 gene polymorphism and prostate cancer risk: A meta-analytic study

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