ライフサイエンスコーパス: NOX5

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

2 a novel mechanism governing the activity of Nox5.

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

4 ocalizes in the same cellular compartment as NOX5.

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

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

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

8 0 is a covalent inhibitor of mainly NOX2 and NOX5.

9 dependent, in line with it being mediated by Nox5.

10 -binding domains of Cylindrospermum stagnale NOX5.

11 nteractions between Cav-1/Nox1 but not Cav-1/Nox5.

12 t Ca(2+) induces ROS production in VSMCs via Nox5.

13 Here, we identified type 5 NADPH oxidase (NOX5), a calcium-activated, ROS-forming enzyme, as the m

14 imulations, we decode the molecular basis of NOX5 activation and electron transfer.

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

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

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

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

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

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

21 lanine prevented CAMKII-induced increases in Nox5 activity.

22 dominant-negative, robustly increased basal Nox5 activity.

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

24 Knockdown of NOX5 also significantly decreased retinoblastoma protein

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

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

27 Human VSMCs express Nox1, Nox4, Nox5 and Cav-1.

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

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

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

31 Identifying molecular pathways that control Nox5 and VSMC-derived EVs provides potential targets to

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

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

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

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

36 are resistant to calcification and identify Nox5 as a key regulator of VSMC phenotypic switching.

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

38 Collectively, these findings identify NOX5 as a superior target in human DKD compared with oth

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

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

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

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

43 that act as signaling platforms for Nox1 and Nox5 but not Nox4, in human VSMCs.

44 l fractionation studies showed that Nox1 and Nox5 but not Nox4, localize in cholesterol-rich fraction

45 oparticles indeed contained higher levels of NOX5-but not NOX1, NOX2, or NOX4-with a bimodal distribu

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

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

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

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

50 NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radica

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

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

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

54 the active site of Cylindrospermum stagnale NOX5 (csNOX5).

55 eased calcification, while overexpression of Nox5 decreased contractile marker expression.

56 ium overload increased brain ROS levels in a NOX5-dependent manner.

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

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

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

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

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

62 Short-term acid-induced increase in NOX5 expression and p16 methylation might be reversible,

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

64 appears to be ineffective in the presence of NOX5 expression in diabetes.

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

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

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

68 Colocalization demonstrated Nox5 expression in mesangial cells.

69 Nox5 expression increased in human diabetic glomeruli co

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

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

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

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

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

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

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

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

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

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

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

81 etes, we found increased expression of renal NOX5 in association with enhanced ROS formation and upre

82 role of the NADPH oxidase catalytic subunit NOX5 in cerebral infarction.

83 Mechanistically, mice expressing human Nox5 in endothelial cells developed-upon aging-severe sy

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

85 In vitro, silencing of NOX5 in human mesangial cells attenuated upregulation of

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

87 preclinical models of DKD, overexpression of NOX5 in Nox4-deficient mice enhances kidney damage by in

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

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

90 increased levels of ROS and Ca(2+)-dependent Nox5 in synthetic VSMCs.

91 Using a mouse expressing human NOX5 in the endothelium, the investigators show that NOX

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

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

94 e of the pro-oxidant enzyme NADPH oxidase 5 (NOX5) in DKD, independent of the previously characterize

95 gulated VSMC phenotype as siRNA knockdown of Nox5 increased contractile marker expression and decreas

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

97 We conclude that NOX5-induced uncoupling of endothelial NOS is a causal m

98 Future studies of NOX5 inhibition in humans, particularly in the setting o

99 phosphorylation was attenuated by mellitin (Nox5 inhibitor) and Nox5 siRNA, while p53 phosphorylatio

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

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

102 Nox5 is a novel Nox isoform whose activity is regulated

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

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

105 the endothelium, the investigators show that NOX5 is activated and plays a deleterious role in promot

106 NOX5 is activated by intracellular calcium signaling, bu

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

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

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

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

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

112 Nox5 itself regulated VSMC phenotype as siRNA knockdown

113 me, and functional outcomes were worsened in NOX5-KI mice.

114 Nox5 knock-in (KI) mice represent the first mechanism-ba

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

116 Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular dise

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

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

119 dy we examined whether PPI treatment affects NOX5, microsomal prostaglandin E synthase (mPGES)-1 and

120 d that a unique pharmacological inhibitor of NOX5, ML090, if given early, around the time of reoxygen

121 We found that NADPH oxidase 5 (NOX5), mPGES-1 and iNOS were significantly increased in

122 We conclude that NOX5, mPGES1 and iNOS may be reversible after PPI treatm

123 acid treatment also significantly increased NOX5, mPGES1 and iNOS mRNA expression.

124 -month PPI treatment significantly decreased NOX5, mPGES1 and iNOS.

125 In BAR-T cells, NOX5 mRNA and p16 promoter methylation increased after p

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

127 NOX5 mRNA was also significantly higher in Barrett tissu

128 Four or eight-week-acid induced increase in NOX5 mRNA, NOX5 protein and p16 methylation may be rever

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

130 endent reactive oxygen species (ROS)-forming Nox5 (NADPH oxidase 5).

131 n by molecular network analysis and identify NOX5, not present in rodents, as a sole neighbor to huma

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

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

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

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

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

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

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

139 12 hours, which manifested as an increase in NOX5-positive intramyocardial blood vessels, as well as

140 NOX5 positivity and cellular localization were studied v

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

142 ght-week-acid induced increase in NOX5 mRNA, NOX5 protein and p16 methylation may be reversible.

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

144 and out of lipid rafts/caveolae for Nox1 and Nox5 respectively.

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

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

147 mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling.

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

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

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

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

152 NOX5-S contributes to increased cell proliferation and d

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

179 AS2870), we have discovered a first-in-class NOX5 selective inhibitor through minor functionalization

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

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

182 attenuated by mellitin (Nox5 inhibitor) and Nox5 siRNA, while p53 phosphorylation was inhibited by N

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

184 r a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulat

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

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

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

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

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

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

191 Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogeni

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

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

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

195 NOX5 was found in cardiomyocyte cytoplasm, plasma membra

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

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

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

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