ライフサイエンスコーパス: OCT1

1 OCT1 and OCT2 are involved in renal secretion of cationi

2 OCT1 inhibition decreased AP uptake of pentamidine by ap

3 as HDAC2 to octamer transcription factor 1 (OCT1) (POU2F1) binding sites of the TWIST1 and SLUG prom

4 c variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide

5 metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the inte

6 Organic cation transporter 1 (OCT1) plays a critical role in the hepatocellular uptake

7 Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, b

8 1 encoding the organic cation transporter-1 (OCT1) may affect the response of hepatocellular carcinom

9 is accompanied by the appearance of aberrant OCT1 variants that, together with decreased OCT1 express

10 Both variants abolished OCT1-mediated uptake of tetraethylammonium, a typical OC

11 cytes, but the literature is ambiguous about OCT1 (mOct1) localization, with some evidence suggesting

12 of the CAAT box by an ATF binding site or an OCT1 binding site had no phenotypic effect in an otherwi

13 ment shifted substrate selectivity toward an OCT1-like phenotype.

14 -represented in these genes, as were AP1 and OCT1 sites.

15 61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-G465R) altered evolutionarily conserved amino acid

16 scription, the homeodomain proteins MSX1 and OCT1.

17 th the observed differences between OCT3 and OCT1 and to the mechanisms of substrate recognition by O

18 Because OCT1 interacts with a variety of structurally diverse or

19 29332 metabolites predicted 146 competitive OCT1 ligands, of which an endogenous neurotoxin, 1-benzy

20 Thirty competitive OCT1 ligands, defined as ligands predicted in silico as

21 forms enhance MSX1 repression and counteract OCT1 activation of the GnRH gene.

22 OCT1 variants that, together with decreased OCT1 expression, may dramatically affect the ability of

23 rce optical coherence tomography device (DRI-OCT1 Atlantis; Topcon).

24 We show the transcription factor OCT1 binds TNF(-857T) but not TNF(-857C), and interacts

25 pon the octamer-binding transcription factor OCT1.

26 r assay, and the basal transcription factors OCT1 and SP1 were shown to bind the first and the second

27 001) as was carriage of two reduced-function OCT1 alleles compared with carriage of one or no deficie

28 01) in individuals with two reduced-function OCT1 alleles who were treated with OCT1 inhibitors.

29 the phenotype, carriage of reduced-function OCT1 variants, and concomitant prescribing of drugs know

30 ariants that reduced or eliminated function (OCT1-R61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-

31 A variant with increased function (OCT1-S14F) changed an amino acid residue such that the h

32 In cells expressing functional OCT1 variants, OCT1 inhibition with quinine prevented so

33 function (OCT1-R61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-G465R) altered evolutionarily conse

34 bstrate ASP(+) in cells overexpressing human OCT1.

35 Recent studies have shown that human OCT1 is highly polymorphic.

36 " i.e. the 24 residues that are conserved in OCT1 orthologs as one amino acid and in OCT2 as a differ

37 rmin in the kidney was severely decreased in OCT1/2(-/-) mice when evaluated with [(11)C]-Metformin a

38 Conversely, a reciprocal mutation in OCT1 (F161L) shifted the polyamine-sensitivity phenotype

39 cket of OCT3 to the corresponding residue in OCT1 (L166F, F450L, and E451Q) reduced the rate of MPP(+

40 ansporters, we tested metformin treatment in OCT1/2(-/-) mice.

41 apeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug

42 er prolonged androgen stimulation, including OCT1 and NKX3-1.

43 omitant use of medications, known to inhibit OCT1 activity, was associated with intolerance (odds rat

44 mitant prescribing of drugs known to inhibit OCT1 transport in 251 intolerant and 1,915 fully metform

45 A short hairpin RNA-mediated OCT1 knockdown in Caco-2 cells decreased AP uptake of pe

46 We discuss metformin, OCT1, pharmacogenetics, and how the integrative genomics

47 we identified competitive and noncompetitive OCT1-interacting ligands in a library of 1780 prescripti

48 CR revealed expression of OCT3 mRNA, but not OCT1 or OCT2 mRNA, in the medial hypothalamus.

49 ain reaction detected OCT2 and OCT3, but not OCT1, mRNA expression in CP.

50 Notably, OCT1-420del (allele frequency of about 20% in white Amer

51 Ablation of OCT1 and OCT2 significantly reduced the distribution of

52 Expression of OCT1 and OCT2 in Xenopus oocytes increased hemicholinium

53 Expression of OCT1 variants in Xenopus laevis oocytes and determinatio

54 ppear to be independent of the expression of OCT1/2 and AMPK-beta1, the most abundant AMPK-beta isofo

55 S, competitive and noncompetitive ligands of OCT1 can be predicted.

56 equivocally show AP membrane localization of OCT1 (mOct1) in Caco-2 cells and human and mouse intesti

57 tudy aims at determining the localization of OCT1 (mOct1) in Caco-2 cells, and human and mouse entero

58 l three systems confirmed AP localization of OCT1 (mOct1).

59 liminary findings showing AP localization of OCT1 in Caco-2 cell monolayers, an established model of

60 sions were drawn assuming BL localization of OCT1 in enterocytes.

61 e C-terminal half of the rabbit orthologs of OCT1/2.

62 Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were ide

63 s carrying reduced function polymorphisms of OCT1.

64 ges at evolutionarily conserved positions of OCT1 are strong predictors of decreased function and sug

65 igher sensitivity pharmacological profile of OCT1.

66 ensitivity of OCT3 is different from that of OCT1 and OCT2 but correlates significantly with that of

67 eliminated function (OCT1-R61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-G465R) altered evolutio

68 yeast mitochondrial intermediate peptidase ( OCT1 gene, YMIP polypeptide), a metalloprotease required

69 rmidine, spermine) and polyamine-like potent OCT1 blockers (1,10-diaminodecane, decamethonium, bistri

70 t reduced or eliminated function (OCT1-R61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-G465R) alte

71 Our results suggest that reduced OCT1 transport is an important determinant of metformin

72 te peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing t

73 graphy-dual mass spectrometry confirmed that OCT1 is able to transport sorafenib and that R61S fs*10

74 Collectively, the data indicate that OCT1 is important for metformin therapeutic action and t

75 Further analysis indicated that OCT1 and OCT3 can recognize essentially the same substra

76 tes and elsewhere because it has stated that OCT1 is basolaterally localized in enterocytes.

77 e human protein matched the consensus of the OCT1 mammalian orthologs.

78 The N353L and R403I substitutions (OCT2 to OCT1) did not significantly change the properties of OCT

79 the human liver organic cation transporter, OCT1, in Xenopus oocytes.

80 The organic cation transporter, OCT1, is a major hepatic transporter that mediates the u

81 eviously cloned organic cation transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1).

82 ated uptake of tetraethylammonium, a typical OCT1 substrate, and were not able to induce sorafenib se

83 Functional studies using OCT1-specific substrate pentamidine showed transporter-m

84 n cells expressing functional OCT1 variants, OCT1 inhibition with quinine prevented sorafenib-induced

85 hat the protective effects of metformin were OCT1/2 independent when tested in this model.

86 We investigated whether OCT1 plays a role in the action of metformin and whether

87 on of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug.

88 -function OCT1 alleles who were treated with OCT1 inhibitors.