ライフサイエンスコーパス: NTCP

1 NTCP and OATPs contribute to hepatic uptake of conjugate

2 NTCP could promote HBV RNA transcription, protein expres

3 NTCP from normal human liver (NHL) was first characteriz

4 NTCP inhibition shifts bile salt uptake, which is genera

5 NTCP inhibition using myrcludex B had only moderate effe

6 NTCP is also a target of multiple drugs.

7 NTCP predicts the choice made as a stochastic choice: Th

8 NTCP protein expression in HepG2/NTCP cells, despite bei

9 NTCP, which is expressed in hepatocytes, plays a physiol

10 NTCP-expressing cell lines can be efficiently infected w

11 between the control and HBV-infected Huh7.5-NTCP cells were similar, suggesting that HBV infection d

12 ically changed the gene expression of Huh7.5-NTCP cells.

13 differ significantly from the predicted 8.8% NTCP (based on dose delivered) and excluded a 25% true i

14 Pronounced liver enrichment, active NTCP-mediated targeting of hepatocytes and efficient cel

15 ugh mutagenesis analysis and screening among NTCP orthologues from Old World monkeys, New World monke

16 Our results suggest that an NTCP model can be used prospectively to safely deliver f

17 We used an NTCP model with parameters calculated from our previous

18 nsporter function by targeting IBAT/ASBT and NTCP, there is an array of potentially additive therapeu

19 ically inhibits both HBV internalization and NTCP oligomerization, resulting in inhibition of HBV inf

20 HBV proviral factors: RXRA, POLL, LDLR, and NTCP.

21 sion was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated ch

22 Expression of OATP and NTCP messenger RNA and protein was determined from a ban

23 bject variability in expression of OATPs and NTCP.

24 of targeted nanoparticles were optimized and NTCP-specific, ligand-dependent binding and internalizat

25 overall hepatic uptake of rosuvastatin, and NTCP may be a heretofore unrecognized transporter import

26 for their transport inhibition against ASBT, NTCP, and SOAT.

27 reclinical studies for pharmacological ASBT, NTCP, and/or SOAT inhibition.

28 We further analyzed the association between NTCP oligomerization and HBV internalization, a process

29 An inhibitor of the interaction between NTCP and epidermal growth factor receptor (EGFR), anothe

30 Myrcludex B blocked NTCP transport of bile salts; small hairpin RNA-mediated

31 Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), gener

32 SBT (SLC10A2), the hepatic bile acid carrier NTCP (SLC10A1), and the steroid sulfate carrier SOAT (SL

33 paper we tested the efficacy of four common NTCP models applied quantitatively to sub-clinical X-ray

34 In conclusion, NTCP appeared inefficient to mediate infection by serum-

35 Conclusion: NTCP inhibition increases biliary lipid secretion, which

36 gh-affinity Na+ /taurocholate cotransporter (NTCP) and the BA synthesizing enzyme cholesterol 7 alpha

37 No primary defects in the deduced NTCP amino acid sequence were found.

38 BA transporters, MABA uptake was efficient (NTCP>ASBT>OATP1B3) and inhibitable by TCA.

39 lc10a1-knockout mouse model (Slc10a1 encodes NTCP).

40 orescence-based transport assays to evaluate NTCP and ASBT inhibitors.

41 The Y146A/F274A NTCP mutant did not support in vitro HBV infection, and

42 Four NTCP models, Lyman, Logistic, Weibull and Poisson, were

43 teral (sinusoidal) BA uptake in hepatocytes (NTCP inhibitors).

44 HepG2(NTCP/Cas9) cells were transduced with a pooled lentivira

45 ed primary human hepatocytes (PHH) and HepG2-NTCP cells led to a reduction in viral replication, as e

46 n, DDB2 was knocked out in HepAD38 and HepG2-NTCP cells.

47 nscomplementation of wild-type DDB2 in HepG2-NTCP-DDB2 knockout cells rescued cccDNA formation and it

48 tion was stunted significantly, and in HepG2-NTCP-DDB2 knockout cells, downstream indicators of cccDN

49 ues, alter the recognition of infected HepG2-NTCP by HBV-specific CD8 T cells.

50 TCRs and eliminated HBV from infected HepG2-NTCP cell cultures.

51 Knockdown of DDB2 in HBV-infected HepG2-NTCP cells and primary human hepatocytes (PHH) also resu

52 HBV-infected HepG2-NTCP cells were treated with tenofovir disoproxil fumara

53 Direct exposure of infected HepG2-NTCP to TLR7/8 agonists had no impact on T-cell recognit

54 Exposure of infected HepG2-NTCP to TLR7/8 CM enhanced HBV-specific CD8 T-cell recog

55 scriptome analysis of IFNalpha-treated HepG2-NTCP cells and found that IFI27 was among the most diffe

56 HepG2/NTCP cells released more viral antigens than HepG2 cells

57 sporting polypeptide-transduced HepG2 (HepG2/NTCP) cells.

58 NTCP protein expression in HepG2/NTCP cells, despite being driven by the cytomegalovirus

59 more efficient in HepaRG cells than in HepG2/NTCP cells.

60 ow HBsAg/HBeAg ratio by ccHBV-infected HepG2/NTCP cells was attributable to dimethyl sulfoxide (DMSO)

61 Moreover, HepG2/NTCP cells secreted very little hepatitis B surface anti

62 sed PM-PKC and decreased PM-MRP2 in both HuH-NTCP cells and hepatocytes.

63 AMP, increased MARCKS phosphorylation in HuH-NTCP cells and hepatocytes.

64 ed to increase MARCKS phosphorylation in HuH-NTCP cells transfected with DN-PKC, and this suggested P

65 In HuH-NTCP cells transfected with phosphorylation-deficient MA

66 In HuH-NTCP cells, dominant-negative (DN) PKC reversed TLC-indu

67 solic pMARCKS and decreased PM-MARCKS in HuH-NTCP cells.

68 taurocholate cotransporting polypeptide (HuH-NTCP cells) and in rat hepatocytes.

69 Human NTCP is a specific receptor for HBV and HDV.

70 Human NTCP plays an important role in the entry of hepatitis B

71 mined a cryo-EM structure of BLV-bound human NTCP.

72 showed significant transport rates for human NTCP, mouse mNtcp, and mouse mAsbt, human ASBT only show

73 identified 2 short-sequence motifs in human NTCP that were required for species-specific binding and

74 otide primers specific for rat ntcp or human NTCP transcripts revealed only the presence of the rat n

75 impedes NTCP oligomerization and identified NTCP phenylalanine 274 as a residue essential for this o

76 r essential for HBV internalization, impeded NTCP oligomerization.

77 ic inhibitor of HBV internalization, impedes NTCP oligomerization and identified NTCP phenylalanine 2

78 ed two anti-preS2 neutralizing antibodies in NTCP-reconstituted HepG2 cells, while several naturally

79 d that the clinical phenotype of a defect in NTCP might be hypercholanemia in the relative absence of

80 is known regarding genetic heterogeneity in NTCP.

81 t progeny viral particles were infectious in NTCP-reconstituted HepG2 cells.

82 ither troglitazone nor the F274A mutation in NTCP affects the NTCP-EGFR interaction.

83 ates functionally important polymorphisms in NTCP exist and that the likelihood of being carriers of

84 multiple single nucleotide polymorphisms in NTCP in populations of European, African, Chinese, and H

85 , ISG20 and tetherin, restrict HBV spread in NTCP-expressing hepatoma cells.

86 DNA, while dimethyl sulfoxide could increase NTCP protein level despite transcriptional control by a

87 may mediate choleretic effects by inserting NTCP into the plasma membrane, and nPKCepsilon may media

88 Instead, NTCP inhibition shifts hepatic bile salt uptake from mai

89 whereas the predominant uptake in humans is NTCP mediated.

90 n blotting of RNA from NHL revealed a 1.8-kb NTCP transcript.

91 an(GAT) did not significantly decrease liver NTCP (p = 0.136), indicating that AC offers comparable b

92 to Plan(AC), Plan(GAT) further reduced liver NTCP (p = 0.001), liver EUD (p < 0.001) and right kidney

93 an(FB), Plan(AC) significantly reduced liver NTCP (p = 0.033) in Group B, whereas no difference was o

94 new radiobiologic model to compute the liver NTCP from the microscale dose distribution.

95 Here, we show that Myrcludex B-mediated NTCP inhibition actually causes an increase in biliary c

96 dimethyl sulfoxide (DMSO) in culture medium, NTCP overexpression, and HBV genotype D.

97 In a subset of mice, NTCP deficiency resulted in markedly elevated total seru

98 Expression of human but not mouse NTCP in HepG2 and HuH7 cells conferred a limited cell-ty

99 owed that a mutation at phenylalanine 274 of NTCP (F274A) caused a loss of HBV susceptibility and dis

100 Our analytical approximation of NTCP could help optimise radiotherapy planning, for exam

101 vestigate entry process, the contribution of NTCP oligomerization to HBV internalization was evaluate

102 d BSEP and MDR3 in parallel to a decrease of NTCP and CYP8B1 and an increase of MRP4.

103 Stimulatory effects of NTCP inhibition were maintained in Sr-b1(-/-) mice, elim

104 We consider examples of NTCP in both a simple model of normal cells and in a mod

105 o-associated virus, and stable expression of NTCP in a ccHBV producing cell line increased viral mRNA

106 s study revealed several unusual features of NTCP as an HBV receptor and established conditions for e

107 hysiological bile acid transport function of NTCP.

108 The receptor functions of NTCP and virus entry are blocked, in vitro and in vivo,

109 We describe the identification of NTCP deficiency as a new inborn error of metabolism with

110 The identification of NTCP deficiency confirms that this transporter is the ma

111 s an HBV receptor enabled ccHBV infection of NTCP reconstituted HepG2 cells, although very little hep

112 lts; small hairpin RNA-mediated knockdown of NTCP in HepaRG cells prevented their infection by HBV or

113 The Y146A/F274A mutant of NTCP retained bile acid transport function but showed a

114 ty and disrupted both the oligomerization of NTCP and HBV internalization without affecting viral att

115 Up-regulation of NTCP and CYP7A1 indicate failure to activate small heter

116 duct obstruction leads to down-regulation of NTCP mRNA levels, similar to that observed in rat common

117 xposure prevented SHP-mediated repression of NTCP and Cyp7A1 expression, which lead to increased BA s

118 out mouse model supports the central role of NTCP in hepatic uptake of conjugated BAs and hepatitis B

119 bile acid binding and translocation sites of NTCP, it presents an attractive receptor target site for

120 the physiological bile acid binding sites of NTCP.

121 a bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B,

122 interacts with the lipid-exposed surface of NTCP.

123 lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor's extracellul

124 ns capture the effects of intrinsic noise on NTCP.

125 5 and 126 micromol/L) in these two patients, NTCP messenger RNA (mRNA) and protein expression were qu

126 We performed NTCP-modeling and established dose-response relationship

127 ent taurocholate cotransporting polypeptide (NTCP) allelic variants were also assessed.

128 ium taurocholate cotransporting polypeptide (NTCP) and impaired its bile acid transport activity.

129 Na+-taurocholate cotransporting polypeptide (NTCP) and multidrug resistance-associated protein 2 (MRP

130 (+)/taurocholate cotransporting polypeptide (NTCP) and the intestinal apical sodium-dependent BA tran

131 ium taurocholate cotransporting polypeptide (NTCP) as an HBV receptor enabled ccHBV infection of NTCP

132 ium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled re

133 ium taurocholate cotransporting polypeptide (NTCP) as the low- and high-affinity HBV receptors could

134 dent taurocholic cotransporting polypeptide (NTCP) expression and activity, multidrug resistance-asso

135 ium taurocholate cotransporting polypeptide (NTCP) has recently been reported to be an essential host

136 ium-taurocholate cotransporting polypeptide (NTCP) indicate a Na(+) -dependent bile acid uptake mecha

137 ium taurocholate cotransporting polypeptide (NTCP) is a receptor that is essential for hepatitis B vi

138 +) -taurocholate cotransporting polypeptide (NTCP) mediates uptake of conjugated bile acids (BAs) and

139 ium-taurocholate cotransporting polypeptide (NTCP) receptor, affecting the generation of HBsAg and cc

140 ium taurocholate cotransporting polypeptide (NTCP), a viral entry receptor.

141 (+)/taurocholate cotransporting polypeptide (NTCP), OATP1, OATP2, ABCG5, and ABCG8) in the liver.

142 ium taurocholate cotransporting polypeptide (NTCP), respectively, which can be blocked by anti-S and

143 Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid (BA) uptake into hepato

144 ium taurocholate cotransporting polypeptide (NTCP), the currently accepted HBV receptor.

145 ium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile ac

146 ium taurocholate cotransporting polypeptide (NTCP), while the extracellular HDV genome is not m6A met

147 ium taurocholate cotransporting polypeptide (NTCP).

148 ium taurocholate cotransporting polypeptide (NTCP, encoded by SLC10A1), the recently identified bona

149 Na+-taurocholate cotransporting polypeptide (NTCP, SLC10A1).

150 +) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic upta

151 ium-taurocholate cotransporting polypeptide (NTCP; SLC10A1) on the sinusoidal membrane of hepatocytes

152 ium-taurocholate co-transporter polypeptide (NTCP), encoded by the SLC10A1 gene.

153 um taurocholate co-transporting polypeptide (NTCP) after lentiviral transduction were not more suscep

154 um taurocholate co-transporting polypeptide (NTCP) and the bile salt export pump (BSEP), respectively

155 +)/taurocholate co-transporting polypeptide (NTCP), and for the subsequent internalization of the vir

156 +)-taurocholate co-transporting polypeptide (NTCP).

157 um taurocholate co-transporting polypeptide (NTCP).

158 +)-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, a

159 dium-taurocholate cotransporting polypetide (NTCP; Slc10a1) with Myrcludex B, is expected to limit bi

160 ther metabolic pathways, as well as possible NTCP-related viral-drug interactions.

161 ctron microscopy structures of the myr-preS1-NTCP complex were used to analyze virus-receptor interac

162 hrough in silico modeling and in vitro preS1-NTCP binding assays, we observed that the associated HBV

163 50% normal-tissue complication probability (NTCP) after lobar irradiation of the liver results in hi

164 Normal tissue complication probability (NTCP) models could aid the understanding of dose depende

165 ping normal tissue complication probability (NTCP) models for predicting radiation-induced esophagiti

166 ting normal tissue complication probability (NTCP) models have been proposed for predicting symptomat

167 the normal tissue complication probability (NTCP): a problem arising in the radiation treatment of c

168 lop a neuronal theory of the choice process (NTCP), which takes a subject from the moment in which tw

169 e Na(+)-taurocholate cotransporting protein (NTCP).

170 V inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infecti

171 between HBV PreS1 and its cellular receptor NTCP during viral entry into hepatocytes and confirm the

172 in the gene encoding the HBV entry receptor NTCP and mutations within the receptor-binding region of

173 e to infect human cells via the HBV receptor NTCP (Na(+)/taurocholate cotransporting polypeptide), su

174 le salts are not sufficient to down-regulate NTCP expression, these two patients have abnormal respon

175 demonstrate that REV-ERB directly regulates NTCP-dependent hepatitis B and delta virus particle entr

176 Thus, PKCs, by regulating NTCP trafficking, may also play an important role in hep

177 Remarkably, NTCP*2, a variant known to have a near complete loss of

178 d uptake and fluorescent labeling of several NTCP variants indicated that the sensor can also be used

179 ocholate cotransporting polypeptide SLC10A1 (NTCP) plays a key role in this process as the major tran

180 in mice treated with myrcludex B, a specific NTCP inhibitor.

181 Hepatic steady-state NTCP mRNA levels in a group of 23 pre- and postportoente

182 rus entry, is assumed to specifically target NTCP.

183 eports that identify new compounds targeting NTCP and inhibiting HBV entry.

184 ded in patients treated with drugs targeting NTCP.

185 A number of HBV entry inhibitors targeting NTCP have been reported to date; these inhibitors have f

186 IL-17A, IL-17F, TGF-beta1, alpha-SMA, TGR5, NTCP, OATP1a1, and ileum ASBT and decreased liver IL-10,

187 patients have a defect in a gene other than NTCP that influences hepatic clearance of bile salts.

188 comparative expression arrays confirmed that NTCP, which was previously identified through a biochemi

189 e subfamily G member 5/8 activity given that NTCP inhibition still promoted cholesterol excretion in

190 oxyterminal antipeptide antibody showed that NTCP is a 39-kd polypeptide that is N-glycosylated to a

191 These findings suggest that NTCP oligomerization is initiated downstream of the NTCP

192 Human hepatocyte studies suggested that NTCP alone accounted for approximately 35% of rosuvastat

193 The NTCP obtained is in agreement with the data reported fro

194 e nor the F274A mutation in NTCP affects the NTCP-EGFR interaction.

195 etween myr-preS1 tryptophan 41 (W41) and the NTCP residues tyrosine 146 and phenylalanine 274 (Y146/F

196 Accordingly, the coding region of the NTCP gene of two children with this phenotype was sequen

197 igomerization is initiated downstream of the NTCP-EGFR interaction and then triggers HBV internalizat

198 nd probability estimation for predicting the NTCP for radiation-induced esophagitis, the MLR model de

199 analysis of NHL sections indicated that the NTCP protein is expressed on the basolateral surface of

200 ciated HBV mutations are in proximity to the NTCP variant when bound and together partially increase

201 virus preS1/Myrcludex B binding in vivo; the NTCP-independent hepatic BA uptake machinery maintains a

202 Consistent with this NTCP targeting, antiviral activity of vanitaracin A was

203 ether partially increase binding affinity to NTCP S267F.

204 culture-derived HBV, which was attributed to NTCP overexpression, genotype D virus, and dimethyl sulf

205 ng that troglitazone allosterically binds to NTCP, rather than to the bile acid-binding pocket.

206 of inhibitors that target HBV/HDV docking to NTCP.

207 Binding of HBV to NTCP limits its function, thus promoting compensatory BA

208 binding of the hepatitis B and D viruses to NTCP and thereby inhibits the virus's entry into hepatoc

209 r human hepatic bile acid uptake transporter NTCP, but not rat Ntcp, also transported rosuvastatin.

210 uman sodium-dependent bile acid transporter (NTCP) permits analysis of its expression in human liver

211 utant exhibited reduced binding to wild-type NTCP.

212 In conclusion, the myr-preS1-W41/NTCP-Y146/F274 interaction site, characterized by high b

213 Adiponectin correlated with NTCP and affects Cyp7A1 expression both in vivo and in v

214 ound was suggested to directly interact with NTCP and inhibit its transporter activity.

215 nd that troglitazone directly interacts with NTCP and noncompetitively interferes with NTCP-mediated

216 th NTCP and noncompetitively interferes with NTCP-mediated bile acid uptake, suggesting that troglita

217 Here we present the first patient with NTCP deficiency, who was clinically characterized by mil

218 o host cells after interaction of virus with NTCP remains largely unknown.