Transforming growth factor-beta and tumor necrosis factor-alpha cooperate to induce apoptosis in the oligodendroglial cell line OLI-neu.
As shown previously, transforming growth factor-beta (TGF-beta) plays an important role during the period of developmental cell death in the nervous system. As with neurons, oligodendrocytes are generated in excess and eliminated by apoptosis. The present study was aimed at investigating the possible interaction of TGF-beta with tumor necrosis factor-alpha (TNF-alpha) in the regulation of cell death in oligodendroglial precursor cells and analyzing the underlying signaling mechanisms. We show that both factors induce apoptosis independently, but cooperate when applied together. The investigation of the signaling events revealed an important role of the JNK pathway during induction of apoptosis. TGF-beta seemed to be more efficient at inducing a release in cytochrome c from mitochondria than TNF-alpha. This might be the consequence of decreased Bcl-xL levels observed in cells treated with TGF-beta but not with TNF-alpha. Both factors stimulated caspase-3 activity, which could be inhibited by caspase-8 or caspase-9 inhibitors. Therefore, we conclude that TNF-alpha and TGF-beta affect partially common pathways but also regulate different steps in the apoptotic cascade.
Schuster
Norbert
N
Department of Anatomy and Cell Biology, Medical Faculty, University of Saarland, Homburg/Saar, Germany.
Bender
Herdis
H
Rössler
Oliver G
OG
Philippi
Anja
A
Dünker
Nicole
N
Thiel
Gerald
G
Krieglstein
Kerstin
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051020:bcl-X Protein
D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases