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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2609| Título : | Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols. |
| Creador: | Casasampere M |
| Nivel de acceso: | Open access |
| Palabras clave : | Acilación Ceramidasa Alcalina - deficiencia Ceramidasa Alcalina - genética Ceramidasa Alcalina - metabolismo Animales Ceramidasa - metabolismo Ceramidasa - farmacocinética Cumarinas - farmacocinética Colorantes Fluorescentes - farmacocinética Técnicas de Silenciamiento del Gen Células HCT116 Células HEK293 Células HeLa Humanos Hidrólisis Espectrometría de Masas Ratones Ceramidasa Neutra - deficiencia Ceramidasa Neutra - genética Ceramidasa Neutra -metabolismo Esfingolípidos - metabolismo Relación Estructura-Actividad Especificidad por Sustrato Acylation Alkaline Ceramidase - deficiency Alkaline Ceramidase - genetics Alkaline Ceramidase - metabolism Animals Ceramides - metabolism Ceramides - pharmacokinetics Coumarins - pharmacokinetics Fluorescent Dyes - pharmacokinetics Gene Knockdown Techniques HCT116 Cells HEK293 Cells HeLa Cells Humans Hydrolysis Mass Spectrometry Mice Neutral Ceramidase - deficiency Neutral Ceramidase - genetics Neutral Ceramidase - metabolism Sphingolipids - metabolism Structure-Activity Relationship Substrate Specificity Ceramidas Lípidos Espectrometría de masas Esfingolípidos Enzimología Umbelliferone Alto rendimiento cribado ceramides lipids mass spectrometry sphingolipids enzymology umbelliferone high throughput screening |
| Descripción : | Ceramidases catalyze the cleavage of ceramides into sphingosine and fatty acids. Previously, we reported on the use of the RBM14 fluorogenic ceramide analogs to determine acidic ceramidase activity. In this work, we investigated the activity of other amidohydrolases on RBM14 compounds. Both bacterial and human purified neutral ceramidases (NCs), as well as ectopically expressed mouse neutral ceramidase hydrolyzed RBM14 with different selectivity, depending on the N-acyl chain length. On the other hand, microsomes from alkaline ceramidase (ACER)3 knockdown cells were less competent at hydrolyzing RBM14C12, RBM12C14, and RBM14C16 than controls, while microsomes from ACER2 and ACER3 overexpressing cells showed no activity toward the RBM14 substrates. Conversely, N-acylethanolamine-hydrolyzing acid amidase (NAAA) overexpressing cells hydrolyzed RBM14C14 and RBM14C16 at acidic pH. Overall, NC, ACER3, and, to a lesser extent, NAAA hydrolyze fluorogenic RBM14 compounds. Although the selectivity of the substrates toward ceramidases can be modulated by the length of the N-acyl chain, none of them was specific for a particular enzyme. Despite the lack of specificity, these substrates should prove useful in library screening programs aimed at identifying potent and selective inhibitors for NC and ACER3. |
| Colaborador(es) u otros Autores: | Camacho L Cingolani F Casas J Egido-Gabás M Abad JL Bedia C Xu R Wang K Canals D Hannun Ya Mao C Fabrias G |
| Fecha de publicación : | 2015 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.1194/jlr.D061564 |
| Fuente: | J Lipid Res 56(10):2019-2028 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2609 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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