ライフサイエンスコーパス: ALDH2

1 tasis, the effect of which was alleviated by ALDH2.

2 d provides a lead for the design of improved ALDH2.

3 reases the K(m) for NAD(+), as compared with ALDH2.

4 lial cells infected with wild-type or mutant ALDH2.

5 amination of deposited electron densities of ALDH2.

6 cal significance of NO formation by purified ALDH2.

7 nced deacylation, the rate-limiting step for ALDH2.

8 on each individual kinetic step of ALDH1 and ALDH2.

9 1.16 +/- 0.56, and 0.40 +/- 0.10 microM for ALDH2.

10 found to be heterozygous when genotyped for ALDH2.

11 heast Asia that are genetically deficient in ALDH2.

12 c nucleophile, Cys243, in ALDH3A1 but not in ALDH2.

13 at aortic rings and the function of purified ALDH2.

14 e-binding site of the free enzyme species of ALDH2.

15 of organic nitrates to the catalytic site of ALDH2.

16 oactivation of GTN is catalyzed by cytosolic ALDH2.

17 ALDH2 protein in HeLa cell lines expressing ALDH2*1, ALDH2*2, or both were determined by the rate of

18 7 and is dominant over the wild-type allele, ALDH2*1.

19 ation in both wild-type and ALDH2-deficient, ALDH2*1/*2, heterozygotic knock-in mice.

20 tly, we have solved the crystal structure of ALDH2(*)2 complexed with coenzyme to 2.5A(.) We have als

21 ermediate between those of wild-type and the ALDH2(*)2 enzymes.

22 of structural integrity and low activity in ALDH2(*)2 even when complexed with coenzyme.

23 helix within the coenzyme binding pocket of ALDH2(*)2 is reordered, but the active site is only part

24 mitochondrial aldehyde dehydrogenase (ALDH2) ALDH2(*)2 polymorphism is associated with impaired ethan

25 Consistent with the structural data, ALDH2(*)2 showed a concentration-dependent increase in e

26 These studies indicate that the ALDH2*2 allele exerts its dominant effect both by interf

27 c enzyme, results from inheriting one or two ALDH2*2 alleles.

28 The ALDH2*2 gene encoding the inactive variant form of mitoc

29 ALDH2*2 has an increased Km for its coenzyme, NAD+, and

30 t on the enzyme activity, we now report that ALDH2*2 heterozygotes had lower levels of ALDH2 immunore

31 -1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is f

32 A nearly inactive form of the enzyme, ALDH2*2, is found in about 40% of the East Asian populat

33 otein in HeLa cell lines expressing ALDH2*1, ALDH2*2, or both were determined by the rate of loss of

34 The ALDH2*2-encoded subunit (ALDH2K) reduces the activity of

35 ere we report the 2.1 A crystal structure of ALDH2*2.

36 in aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2.

37 ucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype.

38 mimic the protective effects afforded by the ALDH2-2 phenotype.

39 liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or a

40 ncy in mitochondrial aldehyde dehydrogenase (ALDH2), a tetrameric enzyme, results from inheriting one

41 Pregnant mice lacking Aldh2, a key enzyme that detoxifies reactive aldehydes,

42 eceptors, which triggers PKCepsilon-mediated ALDH2 activation in cardiac mast cells, contributing to

43 Furthermore, ALDH2 activation inhibited degranulation and renin relea

44 n HMC-1, and PKCepsilon inhibition prevented ALDH2 activation.

45 Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type

46 ion in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in c

47 hibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 activity.

48 Mitochondrial aldehyde dehydrogenase (ALDH2) activity is produced at low levels in many tissue

49 liver mitochondrial aldehyde dehydrogenase (ALDH2) activity than do other people.

50 from each participant for genotyping at the ALDH2, ADH2, and ADH3 loci.

51 ight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.

52 screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an

53 common mitochondrial aldehyde dehydrogenase (ALDH2) ALDH2(*)2 polymorphism is associated with impaire

54 problems associated with mutations of ALDH1, ALDH2, ALDH4, ALDH10 and succinic semialdehyde (SSDH) ge

55 mitochondrial aldehyde dehydrogenase type-2 (ALDH2) also mimicked and prevented, respectively, the ca

56 in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol co

57 ingle nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P

58 s encoding cytosolic ALDH1 and mitochondrial ALDH2 and ALDH5 were disrupted in the genome of strain T

59 activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxida

60 pt ALDH16A1), including ABCG2, SLC2A9, GCKR, ALDH2 and CNIH2, were replicated.

61 our psoralen and coumarin derivatives toward ALDH2 and compared them to the ALDH2 inhibitor daidzin f

62 s, as measured by Aldefluor stain, is due to Aldh2 and correlates with this protection.

63 e the potency and selectivity for ALDH1A1 or ALDH2 and generate chemical probes to examine the unique

64 ree-dimensional structures of wild-type (WT) ALDH2 and of a triple mutant of the protein that exhibit

65 stimation (utilizing interaction of rs671 in ALDH2 and sex as an instrument) strengthens causal infer

66 eruraria lobata), is a specific inhibitor of ALDH2 and suppresses ethanol consumption.

67 The inactive aldehyde dehydrogenase (ALDH2) and the super-active alcohol dehydrogenase (ADH2)

68 exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1.

69 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIG

70 ated that DPI binds to the catalytic site of ALDH2, and this was confirmed by experiments showing sub

71 Our data identify ALDH2 as highly sensitive target of DPI and explain inhi

72 e of a mitochondrial aldehyde dehydrogenase (ALDH2) as a model.

73 fied mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with red

74 ysis with the aldehyde dehydrogenase 2 gene (ALDH2) as an instrumental variable to examine the associ

75 The inhibition of ALDH1 and activation of ALDH2 at pH 7.4 are due to their different rate-limiting

76 lude mitochondrial aldehyde dehydrogenase 2 (ALDH2), ATP synthase, acyl-CoA dehydrogenase, 3-ketoacyl

77 , acetaldehyde-catabolism-competent mothers (Aldh2(+/-)) can support the development of double-mutant

78 ve previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about

79 The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient

80 Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin (gly

81 Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antiangin

82 Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antiangin

83 r isolated aortas with adenovirus containing ALDH2 cDNA with or without the mitochondrial signal pept

84 ng on the cofactor used, while mitochondrial ALDH2 contributed the rest.

85 ion approach to correct for this bias in our ALDH2 data and, also, to explore the effect of bias on t

86 However, the role of ALDH2 deficiency in the pathogenesis of alcoholic liver

87 lar localization of ALDH2 using immortalized ALDH2-deficient aortic smooth muscle cells and mouse aor

88 Overexpression of ALDH2 in the cytosol of ALDH2-deficient aortic smooth muscle cells led to a sign

89 Infection of ALDH2-deficient aortic smooth muscle cells or isolated a

90 dent from causing hepatocyte death, and that ALDH2-deficient individuals may be resistant to steatosi

91 e ethanol intoxication in both wild-type and ALDH2-deficient, ALDH2*1/*2, heterozygotic knock-in mice

92 uch mutation is in aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2.

93 nce that the pattern of genetic variation at ALDH2 differs from that expected under a standard neutra

94 ts suggest that transgenic overexpression of ALDH2 effectively antagonizes chronic alcohol intake-eli

95 ded subunit (ALDH2K) reduces the activity of ALDH2 enzyme in cell lines expressing the wild-type subu

96 ncy allele for the aldehyde dehydrogenase 2 (ALDH2) enzyme, a critical protein involved in the metabo

97 ose from restriction enzyme digestion of the ALDH2 exon 12 functional polymorphism (Glu-487-Lys) in 1

98 Remarkably, transferring Aldh2(-/-)Fanca(-/-) embryos into wild-type mothers supp

99 Here we report that aged Aldh2(-/-) Fancd2(-/-) mutant mice that do not develop l

100 Lastly, Aldh2(-/-)Fancd2(-/-) mice spontaneously develop acute l

101 an support the development of double-mutant (Aldh2(-/-)Fancd2(-/-)) mice.

102 nd not more mature blood precursors, require Aldh2 for protection against acetaldehyde toxicity.

103 glucose) and identified several cis-eGenes (ALDH2 for systolic and diastolic blood pressure, MCM6 an

104 tely 40-50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after a

105 Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, w

106 We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the asso

107 s associated with the E2 isozyme (product of aldh2 gene) of aldehyde dehydrogenase.

108 ADH6, and ADH7 genes), 4 markers within the ALDH2 gene, and 38 unlinked ancestry-informative markers

109 d reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to

110 Inhibition of ALDH2 has hence become a possible strategy to treat alco

111 However, the ALDH2 hypothesis has not been reconciled with early stud

112 at ALDH2*2 heterozygotes had lower levels of ALDH2 immunoreactive protein in autopsy liver samples.

113 The structure of daidzin/ALDH2 in complex at 2.4 A resolution shows the isoflavon

114 tection and the increased phosphorylation of ALDH2 in females, but had no effect in males.

115 ovide new evidence for the essential role of ALDH2 in GTN bioactivation and may have implications to

116 Overexpression of ALDH2 in the cytosol of ALDH2-deficient aortic smooth mu

117 , but the generation and functional roles of ALDH2 in the oesophagus remain elusive.

118 flanking the aldehyde dehydrogenase 2 locus, ALDH2, in populations of Japanese alcoholics and control

119 t eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC.

120 atives toward ALDH2 and compared them to the ALDH2 inhibitor daidzin for selectivity against five ALD

121 Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorelaxation in

122 e intact maternal aldehyde catabolism, fetal Aldh2 is essential for hematopoiesis.

123 ow that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development of Fancd2(-/-) em

124 Quantitative Western blotting revealed that ALDH2 is mainly cytosolic in mouse aorta and human coron

125 ALDH2 is produced in various tissues including the liver

126 The homotetramer (ALDH1 or ALDH2) is a dimer of dimers (A-B + C-D).

127 Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and

128 Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that metabolizes acetaldehyde

129 Mitochondrial aldehyde dehydrogenase (ALDH2) is the major enzyme that oxidizes ethanol-derived

130 n against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isozymes as well as other dehydrogenases such as H

131 uding compound 36, a selective inhibitor for ALDH2 (Ki = 2.4 muM), and compound 32, which was 10-fold

132 both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetald

133 inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathw

134 xyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol

135 e-2'-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown h

136 m) and mitochondrial aldehyde dehydrogenase (ALDH2, low Km) in Escherichia coli and purified the enzy

137 control populations would have detected the ALDH2 marker as a putative QTL.

138 Wild-type FVB and ALDH2 mice were placed on a 4% alcohol diet or a control

139 anol-treated precision-cut liver slices from ALDH2(-/-) mice and in Kupffer cells isolated from ethan

140 ALDH2(-/-) mice are resistant to ethanol-induced steatos

141 Compared with wild-type mice, ethanol-fed ALDH2(-/-) mice had higher levels of malondialdehyde-ace

142 cription 3 (STAT3) was higher in ethanol-fed ALDH2(-/-) mice than in wild-type mice.

143 d in Kupffer cells isolated from ethanol-fed ALDH2(-/-) mice than those levels in wild-type mice.

144 Finally, ethanol-fed ALDH2(-/-) mice were more prone to CCl4 -induced liver i

145 In the present study, wild-type and ALDH2(-/-) mice were subjected to ethanol feeding and/or

146 eased steatosis and hepatocellular damage in ALDH2(-/-) mice.

147 oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) a

148 to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fo

149 lar smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-

150 r the KCNQ1 (rs2237892, P = 9.29 x 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 x 10(-11); rs12229654, P = 4

151 elihood from genotypes at six closely linked ALDH2 nucleotide substitutions.

152 The F statistic was 77 for ALDH2 on alcohol use, suggesting little weak-instrument

153 some 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms

154 prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol depe

155 overexpression of aldehyde dehydrogenase-2 (ALDH2) on chronic alcohol ingestion-induced myocardial d

156 Aldehyde dehydrogenase 2 (ALDH2), one of 19 ALDH superfamily members, catalyzes th

157 sociations exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a group of

158 ldehyde, an alcohol catabolite detoxified by ALDH2, precipitates similar effects.

159 periments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal ker

160 e, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice.

161 decreased transcriptional activity from the ALDH2 promoter approximately 50% in reporter gene assays

162 Thus, the proximal ALDH2 promoter was bound by NF-Y/CP1 and this transcript

163 orm of mitochondrial aldehyde dehydrogenase (ALDH2) protects nearly all carriers of this gene from al

164 The half-lives of ALDH2 protein in HeLa cell lines expressing ALDH2*1, ALD

165 d aldehyde adducts, and that an activator of ALDH2 reduced I/R injury in males but had no significant

166 ALDH2 reduced the chronic alcohol ingestion-induced elev

167 tructures of the triple mutant and wild-type ALDH2 reflect binding of GTN to the catalytic site and t

168 and may have implications to other fields of ALDH2 research, such as hepatic ethanol metabolism and c

169 Cytosolic overexpression of ALDH2 restored GTN-induced relaxation and GTN denitratio

170 C expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation,

171 results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when exa

172 ng to have a structure very similar to human ALDH2, scallop Omega-crystallin was enzymatically inacti

173 Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxygua

174 When given together with the ALDH2-specific activator, Alda-1, Alda-89 reduced acetal

175 0(3) s-1 M-1 ALDH1-sulfone, ALDH1-sulfoxide, ALDH2-sulfone, and ALDH2-sulfoxide, respectively.

176 sulfone, ALDH1-sulfoxide, ALDH2-sulfone, and ALDH2-sulfoxide, respectively.

177 ty of 55% equivalent to a >90% inhibition in ALDH2 synthesis.

178 In ALDH2, the 3-keto group is surrounded by the adjacent Cy

179 gate the causes of linkage disequilibrium in ALDH2, the gene that encodes aldehyde dehydrogenase 2.

180 liver mitochondrial aldehyde dehydrogenase (ALDH2) to change from deacylation to hydride transfer.

181 In addition, the ALDH2 transgene significantly attenuated chronic alcohol

182 METHODS AND ALDH2 transgenic mice were produced with the chicken bet

183 affected by the subcellular localization of ALDH2 using immortalized ALDH2-deficient aortic smooth m

184 ALDH2 was not significantly protected from inactivation

185 The commercial ALDH (designated ALDH2) was partially sequenced and appears to be a mitoc

186 es and diplotypes of ADH1A, ADH1B, ADH7, and ALDH2 were associated with AD in European Americans and/

187 Notably, PKCepsilon and ALDH2 were both activated by A(2b)/A(3) receptor stimula

188 the esterase and dehydrogenase activities of ALDH2 were inhibited to the same extent by MeDTC sulfone

189 o solved the structures of a mutated form of ALDH2 where Arg-475 is replaced by Gln (R475Q).

190 useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as dur

191 leles at the CHRNA3-CHRNA5 locus, ADH1B, and ALDH2 with respect to phenotypic traits related to anthr

192 ociations of genetic variants (e.g. rs671 in ALDH2) with such risk factors in women - who drank littl

193 human mitochondrial aldehyde dehydrogenase (ALDH2) yielded an unexpected result: the chemically reas