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1.
Prostaglandins Other Lipid Mediat ; 93(3-4): 109-12, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20678580

RESUMEN

Ceramide kinase (CerK) catalyzes the conversion of ceramide to ceramide 1-phosphate (C1P). We previously revealed that CerK is involved in the activation of mast cells. In this study, we performed an advanced investigation into the role of CerK on the activation of mast cells using CERK-/- mice. Although CERK-/- mice were less prone to exhibiting a passive cutaneous anaphylactic shock (PCA)-reaction compared to wild type (WT) mice, the differences were not significant. In bone marrow-derived mast cells (BMMC) activated by cross-linking antigen (Ag)/IgE, not high, but low concentrations of Ag had a reduced effect on degranulation in BMMC from CERK-/- mice compared to effects on BMMC from WT mice. Similarly, when the BMMCs were activated with calcium ionophore to focus on the downstream signaling of Ca(2+)-elevation, only a low concentration of ionophore had a reduced effect on degranulation in the BMMC from CERK-/- mice compared to the effect on BMMC from WT mice. Furthermore, the CerK inhibitor K1 reduced the differences in degranulation observed between the BMMC from CERK-/- and WT mice in a dose-dependent manner, demonstrating a contribution for CerK and its product C1P in degranulation. Although CerK is not essential for activation of mast cells, especially a potent and acute activation such as a PCA reaction, CerK might act as an modulator for mild and chronic activation of mast cells, thus increasing sensitivity to cytoplasmic Ca(2+).


Asunto(s)
Calcio/metabolismo , Mastocitos/citología , Mastocitos/enzimología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Animales , Células de la Médula Ósea/citología , Degranulación de la Célula/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/deficiencia
2.
Biosci Biotechnol Biochem ; 71(10): 2581-4, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17928690

RESUMEN

In a previous study, we synthesized a novel inhibitor of ceramide kinase, K1. In this study, we determined that inhibition by K1 is non-competitive and that four intact six-membered rings are important to the inhibitory activity. Furthermore, we identified an effective in vivo concentration for K1, at which it did not influence any cellular lipid synthesis other than that of ceramide 1-phosphate (C1P) using RBL-2H3 cells, and found that K1 suppressed the activation of mast cells.


Asunto(s)
Mastocitos/efectos de los fármacos , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Animales , Calcimicina/farmacología , Radioisótopos de Carbono/metabolismo , Línea Celular Tumoral , Cromatografía en Capa Delgada , Relación Dosis-Respuesta a Droga , Ionóforos/farmacología , Cinética , Leucemia Basofílica Aguda/enzimología , Mastocitos/metabolismo , Estructura Molecular , Inhibidores de Proteínas Quinasas/química , Ratas
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