RESUMEN
Herein we report that the prosurvival sphingolipid sphingosine 1-phosphate regulates the activities of both Bad and Bax during apoptosis of Jurkat cells. First, sphingosine 1-phosphate treatment results in Bad inactivation via the ERK/Rsk-1 pathway. Second, sphingosine 1-phosphate blocks the translocation of Bax to the mitochondria induced by Fas ligation. MEK inhibition by PD98059 or U0126 not only abrogates sphingosine 1-phosphate-induced Bad phosphorylation, but also its cytoprotective effect. Furthermore, inhibition of both mitochondrial cytochrome c efflux and Bax translocation to the mitochondria by sphingosine 1-phosphate could be overcome by PD98059 or U0126. Hence, the MEK/ERK pathway seems to be crucial for the survival effects initiated by sphingosine 1-phosphate.
Asunto(s)
Apoptosis/fisiología , Lisofosfolípidos/administración & dosificación , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Esfingosina/análogos & derivados , Proteína X Asociada a bcl-2/metabolismo , Proteína Letal Asociada a bcl/metabolismo , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Humanos , Células Jurkat , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Esfingosina/administración & dosificaciónRESUMEN
The sphingolipid ceramide has recently emerged as a new transducer or modulator of apoptotic cell death. This function, however, has recently been challenged. Here, in the light of recent observations, the role of ceramide in apoptosis signaling is discussed.