アシルスフィンゴシン
English Journal
- Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.
- Dyment D1, Sell E, Vanstone M, Smith A, Garandeau D, Garcia V, Carpentier S, Le Trionnaire E, Sabourdy F, Beaulieu C, Schwartzentruber J, McMillan H; FORGE Canada Consortium, Majewski J, Bulman D, Levade T, Boycott K.Author information 1Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.AbstractSpinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N-acylsphingosine amidohydrolase (acid ceramidase) 1 ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic-absence seizures. An extensive genetic and metabolic work-up was unable to arrive at a molecular diagnosis. Whole exome sequencing (WES) identified two rare, deleterious mutations in the ASAH1 gene: c.850G>T and c.456A>C. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the WES and the functional studies prompted an EMG study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of SMA-PME caused by novel mutations in ASAH1 and highlight the clinical utility of WES for rare, intractable forms of epilepsy.
- Clinical genetics.Clin Genet.2013 Oct 25. doi: 10.1111/cge.12307. [Epub ahead of print]
- Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N-acylsphingosine amidohydrolase (acid ceramidase) 1 ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic
- PMID 24164096
- Ceramide galactosyltransferase (UGT8) as a molecular marker of canine mammary tumor malignancy.
- Nowak M1, Dziegiel P, Madej J, Ugorski M.Author information 1Department of Pathology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50–375 Wroclaw, Poland. marcin.nowak@up.wroc.plAbstractThirty-two canine mammary tubulopapillary carcinomas and 14 simple adenomas were studied by immunohistochemistry for the expression of UDP-galactose:ceramide galactosyltransferase (UGT8). The majority of tissue specimens (57%) representing adenomas had no or weak reaction with anti-UGT8 antibodies (0-2 pts according to IRS scale) in comparison to the majority of carcinomas (90%) which stained with high intensities (3-9 pts according to IRS scale). When the average values of the reaction intensities (IRS) for malignant and benign tumors were compared, using the Mann-Whitney U-test, significant differences in UGT8 expression between them were found (P < 0.001). Mammary tubulopapillary carcinomas were further analyzed by IHC and the same rabbit polyclonal antibody directed against UGT8 according to their malignancy grade. It was found that the level of UGT8 increased in tumor specimens together with their grading. A comparison of the average values of the reaction intensity (IRS scale) revealed a significant difference (Mann-Whitney U-test, P < 0.05) in UGT8 expression between tumors representing malignancy grades G3 and G1. Based on the obtained results, it is proposed that UGT8 is associated with malignancy of canine mammary gland cells and may have a potential value as a diagnostic marker.
- Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society.Folia Histochem Cytobiol.2013;51(2):164-7. doi: 10.5603/FHC.2013.0024.
- Thirty-two canine mammary tubulopapillary carcinomas and 14 simple adenomas were studied by immunohistochemistry for the expression of UDP-galactose:ceramide galactosyltransferase (UGT8). The majority of tissue specimens (57%) representing adenomas had no or weak reaction with anti-UGT8 antibodies (
- PMID 23907947
- The lifetime of UDP-galactose:ceramide galactosyltransferase is controlled by a distinct endoplasmic reticulum-associated degradation (ERAD) regulated by sigma-1 receptor chaperones.
- Hayashi T1, Hayashi E, Fujimoto M, Sprong H, Su TP.Author information 1Cellular Stress Signaling Unit, Integrative Neuroscience Branch, Intramural Research Program, NIDA, National Institutes of Health, Baltimore, Maryland 21224, USA. thayashi2r@gmail.comAbstractThe glycosphingolipid biosynthesis is initiated by monoglycosylation of ceramides, the action of which is catalyzed either by UDP-glucose:ceramide glucosyltransferase or by UDP-galactose:ceramide galactosyltransferase (CGalT). CGalT is expressed predominantly at the endoplasmic reticulum (ER) of oligodendrocytes and is responsible for synthesizing galactosylceramides (GalCer) that play an important role in regulation of axon conductance. However, despite the importance of ceramide monoglycosylation enzymes in a spectrum of cellular functions, the mechanism that fine tunes activities of those enzymes is largely unknown. In the present study, we demonstrated that the sigma-1 receptor (Sig-1R) chaperone, the mammalian homologue of a yeast C8-C7 sterol isomerase, controls the protein level and activity of the CGalT enzyme via a distinct ER-associated degradation system involving Insig. The Sig-1R forms a complex with Insig via its transmembrane domain partly in a sterol-dependent manner and associates with CGalT at the ER. The knockdown of Sig-1Rs dramatically prolonged the lifetime of CGalT without affecting the trimming of N-linked oligosaccharides at CGalT. The increased lifetime leads to the up-regulation of CGalT protein as well as elevated enzymatic activity in CHO cells stably expressing CGalT. Knockdown of Sig-1Rs also decreased CGalT degradation endogenously expressed in D6P2T-schwannoma cells. Our data suggest that Sig-1Rs negatively regulate the activity of GalCer synthesis under physiological conditions by enhancing the degradation of CGalT through regulation of the dynamics of Insig in the lipid-activated ER-associated degradation system. The GalCer synthesis may thus be influenced by sterols at the ER.
- The Journal of biological chemistry.J Biol Chem.2012 Dec 14;287(51):43156-69. doi: 10.1074/jbc.M112.380444. Epub 2012 Oct 26.
- The glycosphingolipid biosynthesis is initiated by monoglycosylation of ceramides, the action of which is catalyzed either by UDP-glucose:ceramide glucosyltransferase or by UDP-galactose:ceramide galactosyltransferase (CGalT). CGalT is expressed predominantly at the endoplasmic reticulum (ER) of oli
- PMID 23105111
Japanese Journal
- Pharmacodynamics and Tumoricidal Effect of Adriamycin Entrapped in Ceramide Sulfate-Containing Liposomes.
- 野田 倫,小笠原 富夫,飯田 貴史,山川 秀史,道下 久,三谷 隆彦,黒野 昌庸,八木 國夫
- Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ 17(9), 1246-1250, 1994
- … Ceramide sulfate (N-acylsphingosine-1-O-sulfate), which lacks the galactose residue of sulfatide, was examined as a possibly preferable constituent of liposomes for drug delivery. …
- NAID 110003666197
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