ライフサイエンスコーパス: ADPR

1 ADPR and ADP caused membrane hyperpolarization that, lik

2 ADPR binds to the TRPM2 C-terminal NUDT9-H domain, activ

3 ADPR hydrolysis experiments conducted in the presence of

4 ADPR like its precursor, beta-NAD(+), mimicked the effec

5 ADPR's breakdown product adenosine monophosphate (AMP) s

6 ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from

7 ADPR-cyclase in VSMC membranes was more sensitive than C

8 We conclude the following: (1) ADPR-cyclase in VSMCs has enzymatic properties distinct

9 vity to inhibition by Zn(2+) and Cu(2+); (2) ADPR-cyclase in VSMCs is upregulated by various retinoid

10 Zn(2+) stimulated the activity of CD38 HL-60 ADPR-cyclase and other known types of ADPR-cyclases.

11 membranes was more sensitive than CD38 HL-60 ADPR-cyclase to inactivation by N-endoglycosidase F and

12 In this study we characterize 8-bromo (8Br)-ADPR, a novel compound that specifically inhibits ADPR-a

13 ors of ADPR-gated calcium entry, such as 8Br-ADPR, have the potential to be used as anti-inflammatory

14 Using 8Br-ADPR, we demonstrate that ADPR controls calcium influx a

15 lated proteins, nicotinamide and 2'-O-acetyl-ADPR.

16 degrade NAD to ADP-ribose (ADPR), and adding ADPR to T cells leads to slow but not rapid cell death.

17 An ADPR analog, alpha-beta-methylene-ADPR (AMPCPR), was sho

18 m of deacetylation is proposed to involve an ADPR-peptidylimidate, whereas the mechanism of ADP-ribos

19 We report here that an ADPR cyclase purified from Aplysia californica readily c

20 TRPM2 activation is independent of ADPR and ADPR-binding sites, both [Ca(2+)](i) and the CaM-binding

21 Both cADPR and ADPR are calcium messengers that can mobilize intracellu

22 lic adenosine 5'-diphosphoribose (cADPR) and ADPR were also present in the superfusates collected dur

23 Exogenous beta-NAD, cADPR, and ADPR (all 100 nm) reduced the release of NE in CMA at 16

24 erve-evoked overflow of beta-NAD, cADPR, and ADPR in vascular and non-vascular smooth muscles, beta-N

25 d-type colons, but responses to beta-NAD and ADPR were completely abolished in P2ry1(-/-) mice.

26 Degradation of beta-NAD(+) and ADPR was greater per unit mass in muscles containing onl

27 alcium release from intracellular stores and ADPR controls cation entry through the plasma membrane c

28 fer from the well-characterized CD38-antigen ADPR-cyclase, expressed in HL-60 cells.

29 is plants, induced expression of the Aplysia ADPR cyclase gene resulted in an increase in ADPR cyclas

30 atively stable covalent intermediate between ADPR and the acetyl oxygen of the acetyllysine-protein s

31 yllysine residue which forms an enzyme-bound ADPR-peptidylimidate intermediate and nicotinamide.

32 Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology

33 talyze an enzyme reaction and produce cADPR, ADPR, and/or nicotinamide.

34 atic properties distinct from "classic" CD38 ADPR-cyclase, especially sensitivity to inhibition by Zn

35 ADPR-cyclase from VSMCs, but not CD38 ADPR-cyclase from HL-60 cells, was inhibited by ganglios

36 which, when expressed in isolation, cleaves ADPR into AMP and ribose-5-phosphate.

37 sors are mediated by CD38 and the consequent ADPR-mediated TRPM2 gating.

38 lates cADPR synthesis by ADP ribose cyclase (ADPR cyclase) in cultured epithelial cells.

39 We investigated whether ADP-ribosyl cyclase (ADPR-cyclase) in rat vascular smooth muscle cells (VSMCs

40 ynthesized from NAD by ADP-ribosyl cyclases (ADPR cyclases).

41 eaving NAD(+) into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide serving as a f

42 nicotinamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR).

43 enosine diphosphate ribose (ADPR) and cyclic ADPR, regulating several processes including calcium sig

44 Similarly, SPN was unable to catalyze cyclic ADPR hydrolysis, and could not catalyze methanolysis or

45 ergistic facilitation by [Ca(2+)](i), cyclic ADPR, H(2)O(2), NAADP, and negative feedback regulation

46 the calcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular si

47 d upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 muM), is more potent than 8-Ph-ADPR (

48 Adenosine 5'-diphosphoribose (ADPR) activates TRPM2, a Ca(2+), Na(+), and K(+) permeab

49 derivative of adenosine 5'-diphosphoribose (ADPR), 1,N6-etheno-ADPR (epsilon-ADPR), at low femtomola

50 G-protein and adenosine 5'-diphosphoribose (ADPR)-activated nonselective cation channel, is also exp

51 by intracellular adenosine diphosphoribose (ADPR) binding to the channel's enzymatic Nudix domain.

52 second messenger, adenosine diphosphoribose (ADPR), and nicotinamide.

53 emonstrate that TRPM2 mutants with disrupted ADPR-binding sites can be activated readily by [Ca(2+)](

54 bosomes complexed with ADP-ribosylated eEF2 (ADPR-eEF2), before and after GTP hydrolysis, providing a

55 croM have a potentiating effect that enables ADPR to gate the channel at nanomolar concentrations.

56 and NAADP lead to mobilization of endogenous ADPR presumably via metabolic conversion.

57 indeed reduced cADPR production but enhanced ADPR production, converting the cyclase to be more CD38-

58 epsilon-ADPR was detected by fluorescence at an excitation wavel

59 epsilon-ADPR was formed by the reaction of ADPR with chloroaceta

60 sphoribose (ADPR), 1,N6-etheno-ADPR (epsilon-ADPR), at low femtomolar concentration range in vascular

61 The detection sensitivity for epsilon-ADPR was approximately 10 fmol.

62 d in the range from 0.0125 to 1 pmol epsilon-ADPR.

63 osine 5'-diphosphoribose (ADPR), 1,N6-etheno-ADPR (epsilon-ADPR), at low femtomolar concentration ran

64 activity in infected neutrophils, and exoST(ADPR-) mutants replicated the DeltaexoST phenotype in vi

65 and hydrogen peroxide (H2O2) can facilitate ADPR-mediated activation of heterologously expressed TRP

66 stablish TRPM2 as a coincidence detector for ADPR and cADPR signaling and provide a functional contex

67 ce the affinity of the C-terminal domain for ADPR.

68 ) and the CaM-binding motif are required for ADPR-mediated TRPM2 gating.

69 n channel that is specifically gated by free ADPR.

70 viously shown to contain NAD glycohydrolase, ADPR cyclase, and cADPR hydrolase activities also utiliz

71 The higher ADPR cyclase activity in response to E2 was due to the i

72 Collectively, these data identify ADPR as a new and important second messenger of mouse ne

73 ADPR cyclase gene resulted in an increase in ADPR cyclase activity and cADPR levels, as well as eleva

74 (0.2 mg/kg per day) prevented an increase in ADPR cyclase.

75 m VSMCs, with anti-CD38 antibodies increased ADPR-cyclase activity; CD38 antigen was detected both in

76 3) administration of atRA and T(3) increases ADPR-cyclase in aorta in vivo.

77 to its nuclear receptors in vivo, increases ADPR cyclase activity in uterus.

78 ne monophosphate (AMP) specifically inhibits ADPR, but not cADPR-mediated gating of TRPM2, whereas th

79 a novel compound that specifically inhibits ADPR-activated cation influx without affecting other key

80 These results indicate that intracellular ADPR regulates calcium entry into cells that express LTR

81 The key iso-ADPR-binding residues we identified are highly conserved

82 PAR) by interacting with iso-ADP-ribose (iso-ADPR), the smallest internal PAR structural unit contain

83 ins with significant similarity to the known ADPR cyclases have been reported in any plant genome dat

84 fferent fluorescence-based assays to measure ADPR cyclase activity in Arabidopsis and found that this

85 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio

86 established by isolation of beta-1- O-methyl-ADPR when methanol was added as a cosolvent.

87 on of methanol which forms alpha-1- O-methyl-ADPR.

88 An ADPR analog, alpha-beta-methylene-ADPR (AMPCPR), was shown to be entirely resistant to hyd

89 ain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9.

90 tivity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated

91 rus, but in liver, brain, or skeletal muscle ADPR cyclase was unchanged.

92 in complex with Mg(2+) and a nonhydrolyzable ADPR analogue, alpha,beta-methylene ADP-ribose, reveals

93 NAD but not ADPR provides the substrate for ADP-ribosyltransferase (

94 sis that cell surface ART-2 uses NAD but not ADPR to attach ADP-ribosyl groups to the cell surface, a

95 nd assaying loss of cADPR or accumulation of ADPR.

96 -NAD(+) and for termination of the action of ADPR are likely to be present near sites of neurotransmi

97 Our results suggest that activation of ADPR cyclase is an early ABA-signaling event partially i

98 but to a much lesser degree than activity of ADPR cyclase.

99 The specific activity of ADPR-cyclase in membranes from VSMCs was >20-fold higher

100 marker, we observe conformational changes of ADPR-eEF2 that are due strictly to GTP hydrolysis.

101 the presence of a range of concentrations of ADPR or AMPCPR, identify TRPM2 as a simple ligand-gated

102 Thus, mechanisms for generation of ADPR from beta-NAD(+) and for termination of the action

103 ute for cADPR synthesis or that a homolog of ADPR cyclase with low similarity might exist in plants.

104 in an approximately Delta + 300% increase of ADPR cyclase activity in extracts from uterus, but in li

105 n of atRA to rats resulted in an increase of ADPR-cyclase activity in aorta ( congruent with+60%) and

106 ne (T(3)) to rats resulted in an increase of ADPR-cyclase activity in aorta ( congruent with+89%), bu

107 -mediated TRPM2 activation is independent of ADPR and ADPR-binding sites, both [Ca(2+)](i) and the Ca

108 Ca(2+)](i) gating of TRPM2 is independent of ADPR.

109 these cells, and indicate that inhibitors of ADPR-gated calcium entry, such as 8Br-ADPR, have the pot

110 The conformation and binding interactions of ADPR substrate are predicted to differ from those observ

111 ought to determine whether the low levels of ADPR cyclase activity reported in Arabidopsis are indica

112 od was applied to quantitate the overflow of ADPR upon electrical field stimulation (8 Hz, 0.3 ms, 15

113 epsilon-ADPR was formed by the reaction of ADPR with chloroacetaldehyde at 80 degrees C and pH 4.0.

114 presence of an etheno ring after reaction of ADPR with chloroacetaldehyde.

115 rase 1 (PARP-1), another potential source of ADPR in some leukocytes.

116 r than PARP-1, may be an important source of ADPR in these cells, and indicate that inhibitors of ADP

117 HL-60 ADPR-cyclase and other known types of ADPR-cyclases.

118 ventricle (+18%), but atRA had no effect on ADPR-cyclases in lungs, spleen, intestinal smooth muscle

119 Adding either NAD or ADPR also triggers a different set of mechanisms, not re

120 it Ca2+ release following conversion to 2'-P-ADPR by the action of canine spleen NAD glycohydrolase.

121 chanism and the existence of a 1'-O-peptidyl-ADPR.Sir2 intermediate.

122 8-Ph-ADPR (5) inhibits Ca(2+) signalling and chemotaxis in hu

123 (86, IC50 = 3 muM), is more potent than 8-Ph-ADPR (5).

124 activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective.

125 olase and base-exchange reactions to produce ADPR and NAADP(+).

126 to rates with dcDNA, which showed product [(ADPR)n] inhibition.

127 is not known whether the other CD38 product, ADPR, also regulates leukocyte trafficking In this study

128 o Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease ver

129 Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, bu

130 -length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 muM), confirming

131 TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology

132 TRPM2 is opened by binding of ADP ribose (ADPR) to its C-terminal cytosolic nudix-type motif 9 (NU

133 inding to PAR and recognizes iso-ADP ribose (ADPR), the linkage between two ADPR units.

134 s of beta-NAD(+) and ATP, namely ADP-ribose (ADPR) and ADP in colonic muscles from cynomolgus monkeys

135 TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that prod

136 of cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR) from its substrate, NAD(+).

137 though TRPM2 can be activated by ADP-ribose (ADPR) in vitro, it was unknown how TRPM2 is gated in viv

138 Escherichia coli ADP-ribose (ADPR) pyrophosphatase (ADPRase), a Nudix enzyme, catalyz

139 NUDT9 gene as a highly specific ADP-ribose (ADPR) pyrophosphatase.

140 The enzyme hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate.

141 Free ADP-ribose (ADPR), a product of NAD hydrolysis and a breakdown produ

142 n complex with three inhibitors: ADP-ribose (ADPR), adenosine 5'-diphosphate (hydroxymethyl)pyrrolidi

143 T cells degrade NAD to ADP-ribose (ADPR), and adding ADPR to T cells leads to slow but not

144 rsion of NAD+ into nicotinamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR).

145 se activity-cleaving NAD(+) into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide

146 de, which increase production of ADP-ribose (ADPR).

147 PR, whereas CD38 produces mainly ADP-ribose (ADPR).

148 ribose (cADPR) and from cADPR to ADP-ribose (ADPR).

149 D primarily to adenosine diphosphate ribose (ADPR) and a small amount of cyclic adenosine diphosphate

150 izes NAD(+) to adenosine diphosphate ribose (ADPR) and cyclic ADPR, regulating several processes incl

151 s also produce adenosine diphosphate ribose (ADPR) and nicotinic acid adenine dinucleotide phosphate

152 mitochondrial adenosine diphosphate ribose (ADPR) or nicotinamide adenine dinucleotide (NAD+).

153 intracellular adenosine diphosphate ribose (ADPR) through a diphosphoribose hydrolase domain in its

154 NAD (and its primary metabolite, ADP-ribose, ADPR) caused transient hyperpolarization responses in wi

155 esponsible for cADPR synthesis, ADP-ribosyl (ADPR) cyclase, is rapidly induced by ABA in both wild-ty

156 int mutations in the ADP ribosyltransferase (ADPR) regions of ExoS or ExoT also impaired proapoptotic

157 ive cation channel both function as specific ADPR pyrophosphatases.

158 l domain retaining essentially full specific ADPR pyrophosphatase activity and a proteolytically labi

159 Using 8Br-ADPR, we demonstrate that ADPR controls calcium influx and chemotaxis in mouse neu

160 agonists can be partially suppressed by the ADPR antagonist adenosine monophosphate (AMP), which sug

161 synchronous substitution mechanism forms the ADPR-peptidylimidate intermediate of the sirtuin deacety

162 Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease c

163 ith the C-terminal cytoplasmic domain of the ADPR-gated calcium channel TRPM2, which exhibits low but

164 cing strains is almost entirely due to their ADPR activities, which subvert the host response by targ

165 ess active than CD38 in hydrolyzing cADPR to ADPR.

166 TRPM2 identified recently are insensitive to ADPR, and their gating mechanisms remain unclear.

167 Degradation of beta-NAD(+) to ADPR and other metabolites appears to be mediated by pat

168 IJPs and hyperpolarization responses to ADPR, but not ADP, were inhibited by the P2Y1 receptor a

169 o-ADP ribose (ADPR), the linkage between two ADPR units.

170 Most of the E2-stimulated uterine ADPR cyclase was associated with membranes.

171 Most importantly, VSMC ADPR-cyclase was inhibited by Zn(2+) and Cu(2+) ions; th

172 2)-Vitamin D(3) (calciferol) stimulated VSMC ADPR-cyclase dose dependently at subnanomolar concentrat

173 agonist 9-cis-retinoic acid-upregulated VSMC ADPR-cyclase; the stimulatory effect of atRA was blocked

174 luding the U937 monocyte cell line, in which ADPR induces large cation currents (designated IADPR) th

175 de that cADPR and NAADP, in combination with ADPR, represent physiological co-activators of TRPM2 tha

176 can regulate TRPM2 activity in synergy with ADPR.