Differential signaling of sphingosine derivatives in U937 human monocytes depends on the degree of N-methylation.
Prostaglandins Other Lipid Mediat
; 86(1-4): 68-72, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18467142
Previously, we studied N,N-dimethyl-D-erythro-sphingosine (DMS)-induced cell death and signaling in U937 human monocytes; we found that DMS-induced sphingosine kinase- and PKC-independent apoptosis. In the present study, we studied apoptotic responses by three N-methyl derivatives of sphingosine: N-monomethyl-D-erythro-sphingosine (MMS), N,N,N-trimethyl-D-erythro-sphingosine (TMS), and D-erythro-sphingosine (SPH). The potency order in the apoptotic response was DMS>or=MMS>TMS>SPH. We compared cellular responses to the derivatives in terms of activities of MAPK signaling molecules, mitochondrial membrane potential (DeltaPsi(m)), and reactive oxygen species (ROS) generation. Our results suggest that the degree of N-methylation affects the apoptosis-inducing capacity and other related responses including MAPK modulation, DeltaPsi(m), and ROS generation. Dimethylation and monomethylation on the C2 amine of sphingosine enhance the apoptotic response; however, trimethylation induces differential modulation of signaling molecules and less cytotoxicity. Our investigation will be useful for understanding the actions of sphingolipids in apoptosis and for developing chemotherapeutics based on DMS structure.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esfingosina
/
Monocitos
/
Transducción de Señal
Límite:
Humans
Idioma:
En
Revista:
Prostaglandins Other Lipid Mediat
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2008
Tipo del documento:
Article
Pais de publicación:
Estados Unidos