Regulation by sphingosine 1-phosphate of Bax and Bad activities during apoptosis in a MEK-dependent manner.
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.
Betito
Susan
S
Inserm U466, Institut Louis Bugnard, BP 84225, 31432 Toulouse Cedex 4, France.
Cuvillier
Olivier
O
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008246:Lysophospholipids / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
C494819:BAD protein, human; C494826:BAX protein, human; D008246:Lysophospholipids; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C060506:sphingosine 1-phosphate; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine