ライフサイエンスコーパス: ceramidase

1 , to inhibit the hydrolytic activity of acid ceramidase.

2 o produce and purify recombinant, human acid ceramidase.

3 s who lack the degradative enzyme galactosyl ceramidase.

4 S. cerevisiae that also encodes an alkaline ceramidase.

5 fied a rat brain membrane-bound nonlysosomal ceramidase.

6 educed transcriptional up-regulation of acid ceramidase.

7 indicate that the purified enzyme is a novel ceramidase.

8 tly explain its original identification as a ceramidase.

9 s dependent on generation of sphingosine via ceramidase.

10 erized functional null mutants of Drosophila ceramidase.

11 mportant signaling lipid, by the activity of ceramidases.

12 s were completely resistant to inhibitors of ceramidases.

13 e degradation due to increased expression of ceramidases.

14 D-e-C(18:1)-ceramide, a common substrate of ceramidases.

15 nerated from the hydrolysis of ceramides via ceramidases.

16 cordingly called acid, neutral, and alkaline ceramidases.

17 +(o) markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation medi

18 CER1 is the human ortholog of mouse alkaline ceramidase 1 that we previously identified.

19 These data indicate that ASAH1 (acid ceramidase 1) and GBA2 (glucocerebrosidase 2) enzymes th

20 Human alkaline ceramidase 2 (ACER2) plays an important role in cellular

21 Here we demonstrate that the human alkaline ceramidase 2 (ACER2), a Golgi enzyme, regulates beta1 ma

22 up-regulated the expression of the alkaline ceramidase 2 (ACER2), and the ACER2 up-regulation decrea

23 We have purified a membrane bound ceramidase 22,300-fold to apparent homogeneity.

24 te that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysi

25 In this study, we identified acid ceramidase (A-CDase) as a general transcription target o

26 The slab gene encodes ceramidase, a central enzyme in sphingolipid metabolism

27 Neutral ceramidase, a key enzyme of sphingolipid metabolism, hyd

28 The expression of acid ceramidase (AC) - a cysteine amidase that hydrolyses the

29 whether physiological hypoxia increased acid ceramidase (AC) expression; and (f) the effect of the AC

30 Acid ceramidase (AC) hydrolyzes ceramides, which are central

31 ulating ulcerative colitis, the role of acid ceramidase (AC) in intestinal inflammation is yet to be

32 Acid ceramidase (AC) is a key regulatory enzyme involved in c

33 Acid ceramidase (AC) is a lysosomal cysteine amidase that con

34 Acid ceramidase (AC) is a lysosomal cysteine hydrolase that c

35 Acid ceramidase (AC) is an intracellular cysteine amidase tha

36 Acid ceramidase (AC) is the lysosomal enzyme that degrades ce

37 utoproteolytic cleavage of the inactive acid ceramidase (AC) precursor into the active heterodimer ex

38 In addition, the acid ceramidase (AC) was also upregulated by Ca2+(o); and its

39 strate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradi

40 yotubes that constitutively overexpress acid ceramidase (AC), an enzyme that catalyzes the lysosomal

41 evealed that desipramine down-regulated acid ceramidase (AC), but not sphingosine kinase, at the prot

42 The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphing

43 that the ceramide-metabolizing enzyme, acid ceramidase (AC), is expressed in human cumulus cells and

44 e gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal storage disorder

45 A and genomic sequences encoding murine acid ceramidase (AC; E.C. 3.5.1.23) have been isolated and ch

46 Herein we report the mechanism of human acid ceramidase (AC; N-acylsphingosine deacylase) cleavage an

47 Interestingly, cells deficient in acid ceramidase (aCDase) also exhibited defects in CCL5 induc

48 Both acidic ceramidase (aCDase) and neutral ceramidase (nCDase) acti

49 ation of ceramide through inhibition of acid ceramidase (aCDase).

50 dentified: 1 acid, 1 neutral, and 3 alkaline ceramidases (ACER1, ACER2, and ACER3).

51 t mutations in the gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal

52 rotective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory s

53 2C11 by IL-1beta in rat hepatocytes and that ceramidase activation provides a "switch" that determine

54 Acid ceramidase activities in skin fibroblasts and EBV-transf

55 IL-1beta increases both acid and neutral ceramidase activities, which appear to be regulated by t

56 n reduces) the basal and IL-1beta-stimulated ceramidase activities.

57 g the pcDNA3.1/His-ceramidase construct, and ceramidase activity (at pH 9.5) increased by 50- and 12-

58 void of any ceramidase activity restored the ceramidase activity and caused an increase in the hydrol

59 have demonstrated that BWA does not exhibit ceramidase activity and that bwa null mutants display no

60 ected, providing an accurate measure of acid ceramidase activity as low as 0.1 pmol/mg protein/h.

61 show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, A

62 Not only alkaline ceramidase activity but also the generation of SPH and S

63 s revealed rapid internalization of the acid ceramidase activity from the hamster cell media but not

64 otein that is responsible for all measurable ceramidase activity in Drosophila.

65 dy reports a new assay method to detect acid ceramidase activity in vitro using Bodipy or lissamine r

66 Instead, D-e-MAPP inhibited alkaline ceramidase activity in vitro with an IC50 of 1-5 microM.

67 Here, we demonstrate that only alkaline ceramidase activity is expressed in erythrocytes and tha

68 Alkaline ceramidase activity is highly expressed in mouse erythro

69 Ceramidase activity is impaired in cells lacking both ad

70 ctively, these results suggest that alkaline ceramidase activity is important for the generation of S

71 The ceramidase activity is low, however, and further studies

72 eful wherever the in vitro detection of acid ceramidase activity is of importance.

73 ocytes have alkaline but not acid or neutral ceramidase activity on D-e-C(18:1)-ceramide, a common su

74 that the yeast gene YPC1 encodes an alkaline ceramidase activity responsible for the breakdown of dih

75 ssion in a yeast mutant strain devoid of any ceramidase activity restored the ceramidase activity and

76 A deficiency of acid ceramidase activity results in the lipid storage disorde

77 m by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of cer

78 show that ADIPOR2 possesses intrinsic basal ceramidase activity that is enhanced by adiponectin.

79 of aPHC in mammalian cells elevated in vitro ceramidase activity toward N-4-nitrobenz-2-oxa-1,3-diazo

80 YPC1 ceramidase activity was confirmed by in vitro studies us

81 , perinuclear distribution, although no acid ceramidase activity was detected in the transfected cell

82 rements resulted (suggesting high endogenous ceramidase activity).

83 ls (Deltaypc1Deltaydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressio

84 nd highly sensitive method to determine acid ceramidase activity, and that it could be useful whereve

85 receptors mediate their effects via a novel ceramidase activity, generating sphingoid base as a seco

86 ADIPOR1 also possesses intrinsic ceramidase activity, so we suspect that the two distinct

87 mouse kidney extracts as the source of acid ceramidase activity, this new method was compared with a

88 sease patient to the same extent as the acid ceramidase activity.

89 Paradoxically, cardiolipin stimulated ceramidase activity.

90 of membranes by activating contiguous acidic ceramidase activity.

91 romoter, ultimately culminating in increased ceramidase activity.

92 and that bwa null mutants display no loss of ceramidase activity.

93 e endoplasmic reticulum although it retained ceramidase activity.

94 e is remarkably homologous to human glucosyl ceramidase, an enzyme involved in the ceramide signallin

95 entrations (that induce AGP) do not activate ceramidase and allow Cer accumulation.

96 Manipulating levels of ceramidase and altering these lipids in spin mutants all

97 vide important new information on human acid ceramidase and further document its central role in sphi

98 ramide synthase, sphingomyelin synthase, and ceramidase and small interfering RNA knockdown of human

99 ALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes

100 se A2 (PLA2) activation, markedly suppressed ceramidase and stimulated SMase activity.

101 mide preceded transient activation of acidic ceramidase and subsequent production of sphingosine, fol

102 effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly dec

103 These studies provide new insights into acid ceramidase and the related lipid hydrolase, acid sphingo

104 r determining the activity and inhibition of ceramidases and may be adapted for quantifying sphingomy

105 iency: Ormdl1, sphingosine kinase-2, neutral ceramidase, and ceramide synthase-5.

106 liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activities.

107 precipitated with acid ceramidase using anti-ceramidase antibodies.

108 f a cDNA encoding for a novel human alkaline ceramidase (aPHC) that hydrolyzes phytoceramide selectiv

109 Ceramidases are enzymes involved in regulating cellular

110 Therefore, ceramidases are key enzymes in the regulation of the cel

111 -transferase [SPT]) and ceramide hydrolysis (ceramidase) are elevated in obese adipose tissues.

112 alysis of sequences homologous to human acid ceramidase (ASAH) revealed a 1233-bp cDNA (previously de

113 Acid ceramidase (ASAH1) plays a pivotal role in regulating th

114 alysis revealed that only expression of acid ceramidase (ASAH1) was increased.

115 Moreover, suppression of expression of acid ceramidase (ASAH1), an enzyme that produces SPH, increas

116 dependence is demonstrated both by in vitro ceramidase assays and in intact hepatocytes using a fluo

117 eport detailed characterization of this acid ceramidase-associated "reverse activity" and provide evi

118 ine ratio increments), suggesting a possible ceramidase block.

119 Blocking acid ceramidase but not sphingosine kinase activity in alveol

120 these discrepancies are due to activation of ceramidase by the low concentrations of IL-1beta ( appro

121 Ceramidases catalyze the conversion of ceramide to sphin

122 rane bSMase-induced ceramide using bacterial ceramidase caused ERM hyperphosphorylation and formation

123 ngosine and sphingosine 1-phosphate (S1P) by ceramidase (CDase) and sphingosine kinase.

124 EK 293 and MCF7 cells using the pcDNA3.1/His-ceramidase construct, and ceramidase activity (at pH 9.5

125 neration in arrestin mutant flies expressing ceramidase correlated with a decrease in ceramide levels

126 sembly of ceramide channels, as initiated by ceramidase, could be accelerated by the direct interacti

127 Ceramidases deacylate ceramides, important intermediates

128 exogenous sphingomyelinase or inhibition of ceramidase decreased SRE-mediated gene expression.

129 autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-ons

130 limits of detection for sphingosine-NDA and ceramidase-derived sphingosine-NDA were 9.6 and 12.3 fmo

131 The activity of the purified ceramidase did not require cations, and it was inhibited

132 YPC1p, aPHC exhibited no reverse activity of ceramidase either in vitro or in cells.

133 Acid ceramidase, expressed in a recombinant SV, decreased int

134 Although ceramidase expression aids the removal of internalized r

135 Ceramidase expression facilitates the endocytic turnover

136 Therefore, the phenotypic consequence of ceramidase expression in photoreceptors is caused by fac

137 beta1-integrins downregulate acid ceramidase expression, resulting in further accumulation

138 Here, we show that expression of ceramidase facilitates the dissolution of incompletely f

139 ha) and 40 (beta)-kDa subunits as human acid ceramidase from natural sources, had an acidic pH optimu

140 We have previously purified a membrane-bound ceramidase from rat brain and recently cloned the human

141 These results indicate that SLAB ceramidase function controls presynaptic terminal sphing

142 We show that secreted ceramidase functions in a cell-nonautonomous manner to m

143 ts showed that the green fluorescent protein-ceramidase fusion protein presented a mitochondrial loca

144 Finally, a green fluorescent protein-ceramidase fusion protein was constructed to investigate

145 Instead, the neutral ceramidase gene CDase encodes the protein that is respon

146 hat: (i) the structure of the murine neutral ceramidase gene is virtually identical to that of the hu

147 y functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby revealing, for t

148 Here we identify a novel human ceramidase (haCER2) that regulates the levels of both sp

149 inhibitor D-e-MAPP, suggesting that alkaline ceramidases have a role in the generation of SPH and S1P

150 Five human ceramidases have been identified: 1 acid, 1 neutral, and

151 We show that these two ceramidases have different substrate specificity, such t

152 nwashing (Bwa) is the only putative alkaline ceramidase homologue present in Drosophila.

153 n cells, and it was a poor inhibitor of acid ceramidase (IC50>500 microM).

154 n mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent

155 Role of neutral ceramidase in colon cancer.

156 everal genes encode for variants of alkaline ceramidase in mammals.

157 Loss of acid ceramidase in myeloid cells suppresses intestinal neutro

158 Overexpression of acid ceramidase in normal human skin fibroblasts also led to

159 ll-nonautonomous function, overexpression of ceramidase in tissues distant from photoreceptors suppre

160 e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation

161 These studies point to an important role for ceramidases in the regulation of endogenous levels of ce

162 Ceramidase inhibition increases the ceramide content of

163 tivation/C20:4 generation; (2) C20:4-induced ceramidase inhibition, coupled with SMase stimulation, m

164 S1P increases were inhibited by the alkaline ceramidase inhibitor D-e-MAPP, suggesting that alkaline

165 strongly by the incubation of cells with the ceramidase inhibitor D-erythro-2-tetradecanoylamino-1-ph

166 TNF-alpha and IL-1beta cross-signaling, the ceramidase inhibitor N-oleoyl ethanolamine (1 microM) or

167 is effect was mimicked by treatment with the ceramidase inhibitor N-oleoyl ethanolamine.

168 -2-(N-myristoylamino)-1-phenyl-1-propanol, a ceramidase inhibitor, and TNFalpha, a homologue of adipo

169 Similarly, exogenous ceramide or the ceramidase inhibitor, B13, induced CD1d gene expression

170 tment of nude mice with B13, the most potent ceramidase inhibitor, completely prevented tumor growth

171 Application of ceramide analogues and ceramidase inhibitors induced rapid cell death through a

172 ults indicate that the Asah2-encoded neutral ceramidase is a key enzyme for the catabolism of dietary

173 These results demonstrate that this novel ceramidase is a mitochondrial enzyme, and they suggest t

174 The Asah2-encoded neutral ceramidase is highly expressed in the small intestine al

175 Furthermore, our results show that secreted ceramidase is internalized and localizes to endosomes.

176 ngosine, a product of ceramide hydrolysis by ceramidase, is capable of destabilizing ceramide channel

177 show that, although BWA is unlikely to be a ceramidase, it is a regulator of sphingolipid flux in Dr

178 Fe did not directly affect HK-2 ceramidase levels.

179 renamed human ASAHL since it is a human acid ceramidase-like sequence), chromosomal location, primer

180 d characterization of a novel mouse alkaline ceramidase (maCER1) with a highly restricted substrate s

181 Similar to other alkaline ceramidases, maCER1 had an alkaline pH optimum of 8.0, a

182 he brush border, suggesting that the neutral ceramidase may be involved in a pathway for the digestio

183 phages have high constitutive levels of acid ceramidase mRNA, protein, and activity.

184 ogues of ceramide on rat brain mitochondrial ceramidase (mt-CDase) were investigated.

185 Acid ceramidase (N-acylsphingosine amidohydrolase) is the lys

186 solated and characterized the murine neutral ceramidase (N-CDase) gene, mapped its chromosomal locati

187 analogs (C2- or C6-ceramide) or inhibitor of ceramidase (N-oleoyl ethanolamine) led to a time- and do

188 sphingosine production using an inhibitor of ceramidase, n-oleoylethanolamine, completely abrogated t

189 Both acidic ceramidase (aCDase) and neutral ceramidase (nCDase) activities declined after L- and H-U

190 adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P<0.01).

191 itochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingos

192 Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabo

193 was markedly decreased in liver from neutral ceramidase (NCDase)-deficient mice.

194 ated analogues of ceramide and inhibitors of ceramidases offer a promising therapeutic strategy with

195 olino-1-propanol (PDMP), which inhibits acid ceramidase or glucosylceramide synthase and then increas

196 an myocardial function; and c) inhibition of ceramidase or nitric oxide synthase attenuates myocardia

197 tion, coupled with an on-tissue digestion by ceramidase or sphingomyelinase.

198 olic conversion, with specific inhibitors of ceramidase or sphingosine kinase, attenuated the expecte

199 In the absence of ceramidase, photoreceptors degenerate in a light-depende

200 I tract raising the possibility that neutral ceramidase plays a detoxifying role against inadvertent

201 Using an acid ceramidase promoter driven luciferase reporter plasmid,

202 veolar macrophages, because there was little ceramidase protein or activity (or sphingosine) in monoc

203 uced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-depe

204 Targeted expression of Drosophila neutral ceramidase rescued retinal degeneration in arrestin and

205 h N-oleoylethanolamine (OE), an inhibitor of ceramidase, results in resistance to DNA damage-induced

206 that highly purified liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activit

207 Sphingosine is generated by the action of ceramidase(s) on ceramide, and alveolar macrophages have

208 Transgenic expression of ceramidase suppresses retinal degeneration in Drosophila

209 uced apoptosis in various organs may involve ceramidases that facilitate the degradation of ceramide.

210 hytoceramidase, the first mammalian alkaline ceramidase to be identified as being specific for the hy

211 hod utilizes purified human recombinant acid ceramidase to completely hydrolyze ceramide to sphingosi

212 Ceramide can be metabolized by ceramidase to sphingosine (Sph), and Sph to sphingosine

213 levels of sphingosine, which is generated by ceramidases upon hydrolysis of ceramide.

214 activity could be co-precipitated with acid ceramidase using anti-ceramidase antibodies.

215 The increase in acid ceramidase was confirmed by expression and activity anal

216 ed sphingolipid pathways and found that acid ceramidase was constitutively overexpressed in leukemic

217 Human acid ceramidase was overexpressed in Chinese hamster ovary ce

218 The high levels of acid ceramidase were specific to alveolar macrophages, becaus

219 interfering RNA knockdown of human alkaline ceramidase, which all increase endogenous ceramide level

220 ces cerevisiae gene YPC1 encodes an alkaline ceramidase with a dual activity, catalyzing both hydroly

221 data suggest that maCER1 is a novel alkaline ceramidase with a stringent substrate specificity and th

222 ore the physiological functions of a neutral ceramidase with diverse cellular locations, we disrupted

223 ly hydrolyzes phytoceramide, whereas the new ceramidase YDC1p hydrolyzes dihydroceramide preferential

224 In mammals, degradation of ceramide by ceramidase yields sphingosine, which is phosphorylated b

225 d on sequence homology to the yeast alkaline ceramidases YPC1p, we report the identification and clon

226 d 32% identity to the Saccharomyces alkaline ceramidases (YPC1p and YDC1p) and the human alkaline phy