ライフサイエンスコーパス: preproinsulin

1 sulin expression on CD8+ T cell responses to preproinsulin.

2 tive differences in CD8+ T cell responses to preproinsulin.

3 o a normally stable reporter gene coding for preproinsulin.

4 to diabetes of NOD mice and suggest that the preproinsulin 1 gene is crucial for the spontaneous deve

5 itution at position 32 on the B chain of the preproinsulin 2 molecule.

6 e, tolerance to transgenically overexpressed preproinsulin 2 substantially reduced the onset and seve

7 In primary hepatocytes the presence of the preproinsulin 3'-UTR led to reduced mRNA levels compared

8 These studies revealed that the preproinsulin 5'-UTR was necessary for glucose stimulati

9 oinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes path

10 We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing

11 Preproinsulin-A(SP24)D also blocks ER exit of coexpresse

12 producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an im

13 increased expression of ER-oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative fol

14 1 diabetes (T1D), insulin and its precursor preproinsulin are major self-antigens targeted by T cell

15 nsulin transgene, alanine at position B16 in preproinsulin (B16:A-dKO mice), do not develop diabetes.

16 prediction algorithms, we identified GAD and preproinsulin candidate epitopes.

17 Insulin is synthesized as preproinsulin containing a signal peptide (SP).

18 t antigen-specific therapies directed toward preproinsulin could have high clinical impact.

19 ed T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWM

20 y better agonists than the wild-type "index" preproinsulin-derived peptide (ALWGPDPAAA) were identifi

21 to type 1 diabetes by regulating intrathymic preproinsulin expression.

22 strategy by which the T1D-triggering antigen preproinsulin fused with the immunoglobulin (Ig)G Fc fra

23 hannel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations b

24 te that leptin inhibits transcription of the preproinsulin gene by altering transcription factor bind

25 but with little or no change in the level of preproinsulin gene expression.

26 crease in hexokinase activity, and increased preproinsulin gene transcription were observed in islets

27 cted changes in gene expression, for example preproinsulin gene, global changes in gene expression co

28 L30M preproinsulin-GFP fluorescence largely associated with t

29 site-directed mutagenesis of cDNA encoding a preproinsulin-green fluorescent protein (GFP) (C-peptide

30 e semi-nested products were characterized as preproinsulin I and II by restriction enzyme digestion a

31 The neurons showed the presence of preproinsulin I and II mRNA using polymerase chain react

32 Thus, we demonstrated the presence of preproinsulin I and II mRNA, insulin receptor mRNA and i

33 owed a band that co-migrated with pancreatic preproinsulin I and II mRNAs, and confirmed the PCR resu

34 ase protection assay using specific cRNA for preproinsulin I and II showed a band that co-migrated wi

35 Preproinsulin I mRNA was present in the 17 and 19 day ge

36 sulin II mRNA was shown within the brain and preproinsulin I mRNA within the retina.

37 re assessed in NOD mice that expressed mouse preproinsulin II from a transgene in K cells and nontran

38 Preproinsulin II mRNA was present in all the gestational

39 In the rat, preproinsulin II mRNA was shown within the brain and pre

40 demonstrate p97's role in pQC processing of preproinsulin in cases of naturally occurring mutations

41 os of circulating unmethylated to methylated preproinsulin (INS) DNA have been suggested to reflect b

42 Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neo

43 gment of the 5' untranslated region (UTR) of preproinsulin (Ins2) mRNA.

44 The signal peptide of preproinsulin is a major source for HLA class I autoanti

45 nd defective ribosomal products derived from preproinsulin messenger RNA.

46 The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent

47 beta-cell line INS-1 on leptin exposure when preproinsulin mRNA expression is stimulated by 25 mM glu

48 ximately 90%, but they showed no decrease in preproinsulin mRNA expression.

49 eterminants in the 3'-UTR that stabilize the preproinsulin mRNA in a pancreatic beta-cell-specific ma

50 is via stimulation of the translation of the preproinsulin mRNA in pancreatic beta-cells.

51 Preproinsulin mRNA increased 64% without leptin and rose

52 A fall in levels of preproinsulin mRNA is detected in vivo in islets of ob/o

53 te that long term nutritional state sets the preproinsulin mRNA level in the beta-cell at which trans

54 In the longer term, when preproinsulin mRNA levels have increased approximately 2

55 that palmitate decreases glucose-stimulated preproinsulin mRNA levels in isolated rat islets, an eff

56 ets to elevated levels of palmitate inhibits preproinsulin mRNA levels in the presence of high glucos

57 (insulin secretion, proinsulin translation, preproinsulin mRNA levels, and total protein synthesis)

58 g insulin secretion, proinsulin translation, preproinsulin mRNA levels, or total protein synthesis.

59 two- to threefold oleate-induced increase in preproinsulin mRNA levels, underscoring the importance o

60 ng glucose stimulation (24 h) also increases preproinsulin mRNA levels.

61 iazoxide does not alter leptin inhibition of preproinsulin mRNA levels.

62 indicating that regulated translation of the preproinsulin mRNA occurs in a pancreatic beta-cell-spec

63 Thus, the untranslated regions of the preproinsulin mRNA play crucial roles in regulating insu

64 Overproduction of NO was reduced, and the preproinsulin mRNA response to free fatty acids was rest

65 an effect that is not mediated by changes in preproinsulin mRNA stability, but is associated with inh

66 UTR was necessary for glucose stimulation of preproinsulin mRNA translation, whereas the 3'-UTR appea

67 Preproinsulin mRNA was 2.9-fold above control levels, an

68 Also, pancreatic preproinsulin mRNA was completely absent in these icv le

69 ions, the untranslated regions (UTRs) of the preproinsulin mRNA were examined for elements that speci

70 ng recombinant adenoviruses that express the preproinsulin mRNA with defined alterations, the untrans

71 ing the translation and the stability of the preproinsulin mRNA.

72 e present study demonstrates the presence of preproinsulin mRNAs within the 15, 17 and 19 day gestati

73 concentrations did not alter MIN6 cell total preproinsulin, PC2, or PC3 mRNA levels.

74 ls, two epitopes, DR0401-restricted modified preproinsulin peptide 78-90(K88S) and zinc transport 8 2

75 igen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6.

76 idate the presentation and immunogenicity of preproinsulin peptides and nuORFs.

77 ding HLA class II and I molecules binding to preproinsulin peptides and T cell receptors, T and B cel

78 5 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible

79 epitope derived from the leader sequence of preproinsulin (PPI) and show that 50% of HLA-A2+ patient

80 hat HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T

81 n [HSA]-fusion products) in combination with preproinsulin (PPI) target antigen peptides.

82 ndritic cells pulsed with islet autoantigens preproinsulin (PPI), GAD65, and IA-2, followed by compet

83 itopes, monocyte-derived DC were pulsed with preproinsulin (PPI), glutamic acid decarboxylase (65-kDa

84 HLA-DQ2, -DQ8, and -DQ2/8 by pulsing DC with preproinsulin (PPI), IA-2, and GAD65.

85 complex class II null background, with human preproinsulin (PPI), proinsulin (PI), and insulin and de

86 -A24 (A*2402)-restricted epitope (peptide of preproinsulin [PPI](15-24), ALWGPDPAAA; or PPI(3-11), LW

87 We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into P

88 nd identified epitopes throughout the entire preproinsulin protein and defective ribosomal products d

89 mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to prepro

90 udied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T ce

91 The frequency of preproinsulin-reactive T cells was significantly higher

92 Only T cells reactive to preproinsulin-related peptides isolated from T1D donors

93 a-cell genes, particularly of those encoding preproinsulin, requires an appropriate euchromatin (or "

94 Recently, missense mutations upstream of preproinsulin's signal peptide (SP) cleavage site were r

95 the IRE1alpha activity impairs processing of preproinsulin signal peptide antigen and its recognition

96 t a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue sample

97 ta suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain, and eight ami

98 INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain, and e

99 tested five disease-causing mutations in the preproinsulin SP on recognition by SRP and on their effe

100 t the SRP subunit, SRP54, interacts with the preproinsulin SP.

101 Using type 1 diabetes patient-derived preproinsulin-specific CD8 T-cell clones recognizing eit

102 We comprehensively examined preproinsulin specificity of CD8 T cells obtained from p

103 If preproinsulin uses SRP-dependent or independent pathways

104 Reactivity to similar regions of preproinsulin was also observed in peripheral blood of a