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1 erized functional null mutants of Drosophila ceramidase.
2 , to inhibit the hydrolytic activity of acid ceramidase.
3 o produce and purify recombinant, human acid ceramidase.
4 s who lack the degradative enzyme galactosyl ceramidase.
5 S. cerevisiae that also encodes an alkaline ceramidase.
6 fied a rat brain membrane-bound nonlysosomal ceramidase.
7 indicate that the purified enzyme is a novel ceramidase.
8 the plasma with anti-ceramide antibodies or ceramidase.
9 educed transcriptional up-regulation of acid ceramidase.
10 amily member IV (PAQR4) as a Golgi-localized ceramidase.
11 tly explain its original identification as a ceramidase.
12 s dependent on generation of sphingosine via ceramidase.
13 mportant signaling lipid, by the activity of ceramidases.
14 s were completely resistant to inhibitors of ceramidases.
15 e degradation due to increased expression of ceramidases.
16 D-e-C(18:1)-ceramide, a common substrate of ceramidases.
17 nerated from the hydrolysis of ceramides via ceramidases.
18 cordingly called acid, neutral, and alkaline ceramidases.
19 transcriptomic analysis identifies alkaline ceramidase 1 (ACER1), a key enzyme in sphingolipid metab
20 +(o) markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation medi
25 Here we demonstrate that the human alkaline ceramidase 2 (ACER2), a Golgi enzyme, regulates beta1 ma
26 up-regulated the expression of the alkaline ceramidase 2 (ACER2), and the ACER2 up-regulation decrea
29 te that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysi
30 study investigates the function of alkaline ceramidase 3 (ACER3)-catalyzed hydrolysis of unsaturated
36 whether physiological hypoxia increased acid ceramidase (AC) expression; and (f) the effect of the AC
37 e present study, smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1(fl/fl)/SM(Cre)
41 ulating ulcerative colitis, the role of acid ceramidase (AC) in intestinal inflammation is yet to be
42 c individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blot
53 utoproteolytic cleavage of the inactive acid ceramidase (AC) precursor into the active heterodimer ex
55 strate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradi
56 yotubes that constitutively overexpress acid ceramidase (AC), an enzyme that catalyzes the lysosomal
57 evealed that desipramine down-regulated acid ceramidase (AC), but not sphingosine kinase, at the prot
59 that the ceramide-metabolizing enzyme, acid ceramidase (AC), is expressed in human cumulus cells and
60 e gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal storage disorder
62 A and genomic sequences encoding murine acid ceramidase (AC; E.C. 3.5.1.23) have been isolated and ch
63 Herein we report the mechanism of human acid ceramidase (AC; N-acylsphingosine deacylase) cleavage an
69 previously demonstrated that inhibiting acid ceramidase (aCDase) increases ceramide in HSCs to amelio
73 t mutations in the gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal
74 rotective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory s
75 2C11 by IL-1beta in rat hepatocytes and that ceramidase activation provides a "switch" that determine
77 IL-1beta increases both acid and neutral ceramidase activities, which appear to be regulated by t
79 g the pcDNA3.1/His-ceramidase construct, and ceramidase activity (at pH 9.5) increased by 50- and 12-
80 void of any ceramidase activity restored the ceramidase activity and caused an increase in the hydrol
81 have demonstrated that BWA does not exhibit ceramidase activity and that bwa null mutants display no
82 ected, providing an accurate measure of acid ceramidase activity as low as 0.1 pmol/mg protein/h.
83 show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, A
85 s revealed rapid internalization of the acid ceramidase activity from the hamster cell media but not
87 dy reports a new assay method to detect acid ceramidase activity in vitro using Bodipy or lissamine r
92 ctively, these results suggest that alkaline ceramidase activity is important for the generation of S
95 ocytes have alkaline but not acid or neutral ceramidase activity on D-e-C(18:1)-ceramide, a common su
96 that the yeast gene YPC1 encodes an alkaline ceramidase activity responsible for the breakdown of dih
97 ssion in a yeast mutant strain devoid of any ceramidase activity restored the ceramidase activity and
99 m by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of cer
100 o receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin bind
101 show that ADIPOR2 possesses intrinsic basal ceramidase activity that is enhanced by adiponectin.
102 of aPHC in mammalian cells elevated in vitro ceramidase activity toward N-4-nitrobenz-2-oxa-1,3-diazo
104 , perinuclear distribution, although no acid ceramidase activity was detected in the transfected cell
105 asing ceramide production by inhibiting acid ceramidase activity was sufficient to upregulate catheps
108 ls (Deltaypc1Deltaydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressio
109 nd highly sensitive method to determine acid ceramidase activity, and that it could be useful whereve
110 receptors mediate their effects via a novel ceramidase activity, generating sphingoid base as a seco
112 mouse kidney extracts as the source of acid ceramidase activity, this new method was compared with a
121 e is remarkably homologous to human glucosyl ceramidase, an enzyme involved in the ceramide signallin
124 vide important new information on human acid ceramidase and further document its central role in sphi
125 with UC2288 prevented the induction of acid ceramidase and inhibited both the formation of PGCC from
126 ng a locus containing Acer2, which encodes a ceramidase and is specifically expressed in the collecti
127 suggest that p21 functions upstream of acid ceramidase and plays an important role in polyploidizati
128 ramide synthase, sphingomyelin synthase, and ceramidase and small interfering RNA knockdown of human
129 ALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes
132 mide preceded transient activation of acidic ceramidase and subsequent production of sphingosine, fol
133 effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly dec
134 These studies provide new insights into acid ceramidase and the related lipid hydrolase, acid sphingo
135 r determining the activity and inhibition of ceramidases and may be adapted for quantifying sphingomy
139 f a cDNA encoding for a novel human alkaline ceramidase (aPHC) that hydrolyzes phytoceramide selectiv
144 alysis of sequences homologous to human acid ceramidase (ASAH) revealed a 1233-bp cDNA (previously de
147 Moreover, suppression of expression of acid ceramidase (ASAH1), an enzyme that produces SPH, increas
149 dependence is demonstrated both by in vitro ceramidase assays and in intact hepatocytes using a fluo
150 eport detailed characterization of this acid ceramidase-associated "reverse activity" and provide evi
153 these discrepancies are due to activation of ceramidase by the low concentrations of IL-1beta ( appro
155 rane bSMase-induced ceramide using bacterial ceramidase caused ERM hyperphosphorylation and formation
157 regulation of IRF8 prevented changes of acid ceramidase, ceramide, and sphingosine in CF epithelial c
159 EK 293 and MCF7 cells using the pcDNA3.1/His-ceramidase construct, and ceramidase activity (at pH 9.5
160 neration in arrestin mutant flies expressing ceramidase correlated with a decrease in ceramide levels
161 sembly of ceramide channels, as initiated by ceramidase, could be accelerated by the direct interacti
164 autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-ons
165 limits of detection for sphingosine-NDA and ceramidase-derived sphingosine-NDA were 9.6 and 12.3 fmo
171 Therefore, the phenotypic consequence of ceramidase expression in photoreceptors is caused by fac
172 F8) and a concomitant downregulation of acid ceramidase expression with CF and an increase of ceramid
175 ha) and 40 (beta)-kDa subunits as human acid ceramidase from natural sources, had an acidic pH optimu
176 We have previously purified a membrane-bound ceramidase from rat brain and recently cloned the human
179 ts showed that the green fluorescent protein-ceramidase fusion protein presented a mitochondrial loca
184 hat: (i) the structure of the murine neutral ceramidase gene is virtually identical to that of the hu
185 y functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby revealing, for t
187 inhibitor D-e-MAPP, suggesting that alkaline ceramidases have a role in the generation of SPH and S1P
193 n mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent
194 ve demonstrated a downregulation of the acid ceramidase in CF epithelial cells resulting in an increa
196 nects to a marked downregulation of the acid ceramidase in human and murine CF epithelial cells.
202 ll-nonautonomous function, overexpression of ceramidase in tissues distant from photoreceptors suppre
203 e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation
205 These studies point to an important role for ceramidases in the regulation of endogenous levels of ce
207 tivation/C20:4 generation; (2) C20:4-induced ceramidase inhibition, coupled with SMase stimulation, m
209 S1P increases were inhibited by the alkaline ceramidase inhibitor D-e-MAPP, suggesting that alkaline
210 strongly by the incubation of cells with the ceramidase inhibitor D-erythro-2-tetradecanoylamino-1-ph
211 TNF-alpha and IL-1beta cross-signaling, the ceramidase inhibitor N-oleoyl ethanolamine (1 microM) or
213 -2-(N-myristoylamino)-1-phenyl-1-propanol, a ceramidase inhibitor, and TNFalpha, a homologue of adipo
216 tment of nude mice with B13, the most potent ceramidase inhibitor, completely prevented tumor growth
218 ults indicate that the Asah2-encoded neutral ceramidase is a key enzyme for the catabolism of dietary
220 These results demonstrate that this novel ceramidase is a mitochondrial enzyme, and they suggest t
221 monstrated that the sphingolipid enzyme acid ceramidase is dispensable for polyploidization upon ther
223 Furthermore, our results show that secreted ceramidase is internalized and localizes to endosomes.
226 ngosine, a product of ceramide hydrolysis by ceramidase, is capable of destabilizing ceramide channel
227 mide axis, which may be countered by neutral ceramidase, is suggested to limit cell motility and meta
228 show that, although BWA is unlikely to be a ceramidase, it is a regulator of sphingolipid flux in Dr
230 renamed human ASAHL since it is a human acid ceramidase-like sequence), chromosomal location, primer
231 d characterization of a novel mouse alkaline ceramidase (maCER1) with a highly restricted substrate s
233 he brush border, suggesting that the neutral ceramidase may be involved in a pathway for the digestio
239 solated and characterized the murine neutral ceramidase (N-CDase) gene, mapped its chromosomal locati
240 analogs (C2- or C6-ceramide) or inhibitor of ceramidase (N-oleoyl ethanolamine) led to a time- and do
241 sphingosine production using an inhibitor of ceramidase, n-oleoylethanolamine, completely abrogated t
242 Both acidic ceramidase (aCDase) and neutral ceramidase (nCDase) activities declined after L- and H-U
244 itochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingos
248 ated analogues of ceramide and inhibitors of ceramidases offer a promising therapeutic strategy with
249 cts of treatment with recombinant human acid ceramidase on inflammation and infection.Methods: Sphing
250 cts of treatment with recombinant human acid ceramidase on sphingolipid profile and inflammatory medi
251 olino-1-propanol (PDMP), which inhibits acid ceramidase or glucosylceramide synthase and then increas
252 an myocardial function; and c) inhibition of ceramidase or nitric oxide synthase attenuates myocardia
254 olic conversion, with specific inhibitors of ceramidase or sphingosine kinase, attenuated the expecte
255 cted protein product belongs to the alkaline ceramidase, PAQR receptor, Per1, SID-1, and TMEM8 (CREST
257 I tract raising the possibility that neutral ceramidase plays a detoxifying role against inadvertent
260 eramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2.
261 veolar macrophages, because there was little ceramidase protein or activity (or sphingosine) in monoc
262 ction of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and int
263 uced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-depe
265 findings establish PAQR4 as Golgi-localized ceramidase required for cellular growth in breast cancer
266 Targeted expression of Drosophila neutral ceramidase rescued retinal degeneration in arrestin and
267 h N-oleoylethanolamine (OE), an inhibitor of ceramidase, results in resistance to DNA damage-induced
268 that highly purified liver mitochondria have ceramidase, reverse ceramidase, and thioesterase activit
269 Sphingosine is generated by the action of ceramidase(s) on ceramide, and alveolar macrophages have
270 golipid metabolism by inducing expression of ceramidase, sphingosine kinases 1/2, and S1P receptors.
273 uced apoptosis in various organs may involve ceramidases that facilitate the degradation of ceramide.
276 hytoceramidase, the first mammalian alkaline ceramidase to be identified as being specific for the hy
277 hod utilizes purified human recombinant acid ceramidase to completely hydrolyze ceramide to sphingosi
283 R deficiency causes a downregulation of acid ceramidase via upregulation of IRF8, which is a central
285 ed sphingolipid pathways and found that acid ceramidase was constitutively overexpressed in leukemic
288 interfering RNA knockdown of human alkaline ceramidase, which all increase endogenous ceramide level
289 induction of p21 and that knockdown of acid ceramidase, which hydrolyzes ceramide, does not interfer
290 ces cerevisiae gene YPC1 encodes an alkaline ceramidase with a dual activity, catalyzing both hydroly
291 data suggest that maCER1 is a novel alkaline ceramidase with a stringent substrate specificity and th
292 ore the physiological functions of a neutral ceramidase with diverse cellular locations, we disrupted
293 ly hydrolyzes phytoceramide, whereas the new ceramidase YDC1p hydrolyzes dihydroceramide preferential
295 d on sequence homology to the yeast alkaline ceramidases YPC1p, we report the identification and clon
296 d 32% identity to the Saccharomyces alkaline ceramidases (YPC1p and YDC1p) and the human alkaline phy