ライフサイエンスコーパス: NOX5

1 a novel mechanism governing the activity of Nox5.

2 m Nox1, Nox2, and Nox3 but not from Nox4 and Nox5.

3 ocalizes in the same cellular compartment as NOX5.

4 tion from Nox1, Nox2, Nox3, and Nox4 but not Nox5.

5 ion from Nox1 and Nox2 but not from Nox4 and Nox5.

6 s or some other lymphoid cell types) express NOX5.

7 -binding domains of Cylindrospermum stagnale NOX5.

8 1, Nox2, and Nox3 enzymes but not in Nox4 or Nox5.

9 We found that Nox5 activity in bovine aortic endothelial cells was sup

10 suggest that CAMKII can positively regulate Nox5 activity via the phosphorylation of Ser475.

11 The ability of PMA to increase Nox5 activity was abolished by calcium chelation and was

12 The ability of CAMKII to increase Nox5 activity was also observed with fixed calcium conce

13 ion of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlate

14 H oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic res

15 lanine prevented CAMKII-induced increases in Nox5 activity.

16 dominant-negative, robustly increased basal Nox5 activity.

17 talytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits

18 Knockdown of NOX5 also significantly decreased retinoblastoma protein

19 Nox5, an EF-hand-containing reactive oxygen species (ROS

20 volvement of the nonphagocytic NADPH oxidase NOX5, an enzyme found in lymphoid tissues, but not in ci

21 , this study provides evidence of a role for Nox5 and its derived ROS in promoting progression of dia

22 idue to regulate subcellular localization of Nox5 and its interaction with PtdIns(4,5)P(2).

23 ime polymerase chain reaction and found that Nox5 and Nox4 are abundantly expressed in cardiac fibrob

24 otide phosphate (NADPH)-dependent oxidase 5 (NOX5), and PTGS2 (COX-2) mediated arachidonic acid metab

25 We found that expression levels of nox1, nox5, and duox are dynamic during the first 2 days of de

26 ion to develop a catalog of nox1, nox2/cybb, nox5, and duox expression in zebrafish during early nerv

27 es of five NOX genes (nox1, nox2/cybb, nox4, nox5, and duox) have been identified in the zebrafish ge

28 These studies identify NOX5 as a novel, calcium-dependent source of ROS in athe

29 pression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxyg

30 heme peroxidase (HPX2) and NADPH oxidase 5 (NOX5) as critical mediators of midgut epithelial nitrati

31 In summary, the phosphorylation of Nox5 at key residues facilitates enzyme activation at lo

32 RL reduced the expression of NOX1, NOX2, and NOX5 but induced the expression of NOX4.

33 on of NOX5-S, but not NOX1, and knockdown of NOX5 by NOX5 small interfering RNA abolished acid-induce

34 n experiments suggested an interaction among NOX5, c-Abl, and H(V)1.

35 that the activity and calcium-sensitivity of Nox5 can also be modulated by direct phosphorylation.

36 vely high and raises the question of whether Nox5 can be sufficiently activated in cells that do not

37 inositide in plasma membrane, binds to human Nox5 causing Nox5 to localize from internal membranes to

38 NOX5 cDNA was higher and H2O2 levels were 4 times higher

39 all interfering RNAs for NOX5 indicated that NOX5 controlled Mo-DC differentiation by regulating the

40 ncreased the proportion of motile sperm in a NOX5-dependent manner.

41 in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motil

42 Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities t

43 imity ligation assay, whereas NOX1, NOX2, or NOX5 did not interact with calnexin.

44 trast to other Nox isoforms, the activity of Nox5 does not require the presence of accessory proteins

45 We examined Nox5 expression and regulation in kidney biopsies from d

46 first time to our knowledge, we demonstrate NOX5 expression in human intramyocardial blood vessels a

47 Stimulation with angiotensin II upregulated Nox5 expression in human podocyte cultures and increased

48 Western blot analysis confirmed NOX5 expression in isolated human cardiomyocytes.

49 Colocalization demonstrated Nox5 expression in mesangial cells.

50 Nox5 expression increased in human diabetic glomeruli co

51 In infarcted hearts, NOX5 expression increased, especially in infarctions >12

52 Furthermore, NOX5 expression was analyzed in vitro by using Western b

53 Moreover, we revealed that NOX5 expression was strongly increased during Mo-DC diff

54 evious studies have shown that the EC(50) of Nox5 for calcium is relatively high and raises the quest

55 Because the Nox5 gene is absent in rodents, we generated transgenic

56 This allows the inactivation of SHP-1 by NOX5-generated ROS and contributes to the maintenance of

57 ngs provide the first evidence that podocyte Nox5 has an important role in impaired renal function an

58 However, the kinases that phosphorylate Nox5 have not been identified, and thus, the goal of thi

59 nce PMA increased the calcium sensitivity of Nox5 in a cell-free assay.

60 ll/mesangial cell-specific overexpression of Nox5 in a mouse model of diabetic nephropathy showed enh

61 e generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+)).

62 Thus, we examined the role of Nox5 in human diabetic nephropathy in human mesangial ce

63 In vitro, silencing of Nox5 in human mesangial cells was associated with attenu

64 t cells altered cell surface localization of Nox5 in parallel with extracellular ROS generation.

65 PMA greatly potentiated the activity of Nox5 in response to low concentrations of ionomycin.

66 eart, but knowledge of the calcium-dependent NOX5 in the heart is lacking.

67 pathy, little is known regarding the role of Nox5 in this context.

68 ve inhibitors and small interfering RNAs for NOX5 indicated that NOX5 controlled Mo-DC differentiatio

69 Depletion of Nox4 but not Nox5 inhibits baseline and TGF-beta1 stimulation of Smad

70 Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and i

71 Nox5 is a novel Nox isoform whose activity is regulated

72 in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent

73 animal models of diabetic nephropathy since Nox5 is absent in the mouse genome.

74 d by 16.2+/-0.8-fold (n=3, P<0.005), whereas Nox5 is downregulated.

75 Nox5 is expressed in a variety of fetal tissues as well

76 Thus, extracellular ROS production by Nox5 is modulated by PtdIns(4,5)P(2) by localizing Nox5

77 Our data show that renal Nox5 is upregulated in human diabetic nephropathy and ma

78 e is a paucity of data about the role of the Nox5 isoform of NADPH oxidase in animal models of diabet

79 siRNA-mediated Nox5 knockdown inhibited angiotensin II-stimulated produ

80 In controls, NOX5 localized to the endothelium of a limited number of

81 homologs of gp91phox, termed Nox3, Nox4 and Nox5, members of a growing family of gp91phox homologs.

82 old in CAD and correlated significantly with NOX5 mRNA levels among subjects.

83 NOX5 mRNA was also significantly higher in Barrett tissu

84 We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human s

85 ulated the time-dependent phosphorylation of Nox5 on Thr(494) and Ser(498).

86 ealed that CAMKII can directly phosphorylate Nox5 on Thr494 and Ser498 as detected by phosphorylation

87 free system, with no effect on Nox2-, Nox4-, Nox5-, or xanthine oxidase-derived reactive oxygen speci

88 These data demonstrate that the NOX5-p22phox complex drives Mo-DC differentiation, and t

89 Nox5(pod+) mice exhibited early onset albuminuria, podoc

90 Subjecting Nox5(pod+) mice to streptozotocin-induced diabetes furth

91 ng human Nox5 in a podocyte-specific manner (Nox5(pod+)).

92 12 hours, which manifested as an increase in NOX5-positive intramyocardial blood vessels, as well as

93 NOX5 positivity and cellular localization were studied v

94 hain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CA

95 Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the ac

96 ox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen.

97 NOX5 RNA was found in the hearts of controls and patient

98 n Barrett's patients bile acids may activate NOX5-S and increase reactive oxygen species (ROS) produc

99 cytosolic Ca2+ and sequential activation of NOX5-S and NF-kappaB in SEG1 cells.

100 d mPGES1 expression depends on activation of NOX5-S and NF-kappaB1 p50.

101 was significantly decreased by knockdown of NOX5-S and overexpression of NOX5-S significantly increa

102 NOX5-S contributes to increased cell proliferation and d

103 We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on s

104 Acid-induced NOX5-S expression and H(2)O(2) production were significa

105 Acid-induced NOX5-S expression depends on an increase in intracellula

106 (siRNA) significantly decreased TDCA-induced NOX5-S expression, H(2)O(2) production, and cell prolife

107 xycholic acid (TDCA) significantly increased NOX5-S expression, hydrogen peroxide (H(2)O(2)) producti

108 TGACGAGA and TGACGCTG were identified in the NOX5-S gene promoter.

109 Overexpression of NOX5-S in Barrett's cells significantly increased H2O2 p

110 olipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid-induced increase in cell proliferati

111 In conclusion, in SEG1 EA cells NOX5-S is overexpressed and mediates acid-induced H(2)O(

112 We have shown that the NADPH oxidase NOX5-S may play an important role in the progression fro

113 ificantly decreased TDCA-induced increase in NOX5-S mRNA and the tail moment.

114 The expression of NOX5-S mRNA was significantly higher in these cells than

115 Knockdown of NOX5-S or NF-kappaB1 p50 by their small interfering RNA

116 erexpression of CREB significantly increased NOX5-S promoter activity.

117 by knockdown of NOX5-S and overexpression of NOX5-S significantly increased TDCA-induced increase in

118 Overexpression of NOX5-S significantly increased the luciferase activity i

119 We found that NOX1 and NOX5-S were the major isoforms of NADPH oxidase in SEG1-

120 Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NO

121 acid treatment increased mRNA expression of NOX5-S, but not NOX1, and knockdown of NOX5 by NOX5 smal

122 n a novel Barrett's cell line overexpressing NOX5-S, IkappaBalpha was significantly reduced, and luci

123 LCgamma2, ERK2 MAP kinase, and NADPH oxidase NOX5-S, thereby contributing to the development of EA.

124 NOX5-S-derived ROS may cause DNA damage, thereby contrib

125 X2-derived PGE2 production may contribute to NOX5-S-mediated cell proliferation in SEG1 cells.

126 However, the mechanism of the acid-induced NOX5-S-mediated increase in cell proliferation is not kn

127 ease in thymidine incorporation occurring in NOX5-S-overexpressing Barrett's cells or induced by acid

128 y depend on the activation of TGR5, CREB and NOX5-S.

129 Knockdown of NOX5 significantly decreased [(3)H]thymidine incorporati

130 variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase

131 X5-S, but not NOX1, and knockdown of NOX5 by NOX5 small interfering RNA abolished acid-induced H(2)O(

132 plasma membrane, binds to human Nox5 causing Nox5 to localize from internal membranes to the plasma m

133 Exposure of cells expressing Nox5 to phorbol 12-myristate 13-acetate (PMA) resulted i

134 intact cells was supported by the binding of Nox5 to phosphoprotein-affinity columns and via MS/MS an

135 ed PtdIns(4,5)P(2)-dependent localization of Nox5 to the plasma membrane and decreased extracellular

136 s modulated by PtdIns(4,5)P(2) by localizing Nox5 to the plasma membrane.

137 an mesangial cells and in an inducible human Nox5 transgenic mouse exposed to streptozotocin-induced

138 Within the cell, Nox5 was detected in detergent-resistant microdomains of

139 NOX5 was expressed in circulating myeloid DC, and at a l

140 Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesio

141 NOX5 was found in cardiomyocyte cytoplasm, plasma membra

142 In human kidney biopsies, Nox5 was identified to be expressed in glomeruli, which

143 Interestingly, NOX5 was localized at the outer membrane of the mitochon

144 tation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blottin

145 The presence of NOX5 was studied via RT-PCR in heart tissue from patient