Transforming growth factor-β and tumor necrosis factor-α cooperate to induce apoptosis in the oligodendroglial cell line OLI-neu

✍ Scribed by Norbert Schuster; Herdis Bender; Oliver G. Rössler; Anja Philippi; Nicole Dünker; Gerald Thiel; Kerstin Krieglstein

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 236 KB
• Volume: 73
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10666

✦ Synopsis

Abstract

As shown previously, transforming growth factor‐β (TGF‐β) 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‐β with tumor necrosis factor‐α (TNF‐α) 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‐β seemed to be more efficient at inducing a release in cytochrome c from mitochondria than TNF‐α. This might be the consequence of decreased Bcl‐xL levels observed in cells treated with TGF‐β but not with TNF‐α. Both factors stimulated caspase‐3 activity, which could be inhibited by caspase‐8 or caspase‐9 inhibitors. Therefore, we conclude that TNF‐α and TGF‐β affect partially common pathways but also regulate different steps in the apoptotic cascade. © 2003 Wiley‐Liss, Inc.