TGF-β induces cell death in the oligodendroglial cell line OLI-neu

✍ Scribed by Norbert Schuster; Herdis Bender; Anja Philippi; Srinivasa Subramaniam; Jens Strelau; Ziyuan Wang; Kerstin Krieglstein

• Book ID: 102845556
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 903 KB
• Volume: 40
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.10110

✦ Synopsis

Abstract

We have shown that TGF‐β plays an important role during the period of developmental cell death in the nervous system. Immunoneutralization of TGF‐β prevents ontogenetic neuron death in vivo. Like neurons, oligodendrocytes are generated in excess and eliminated by apoptosis. It has been shown that oligodendrocyte progenitors and newly formed oligodendrocytes are especially susceptible to apoptosis. We choose the oligodendrocyte precursor cell line OLI‐neu to address the question if TGF‐β could play a role for the control of oligodendrocyte proliferation and cell death. Flow cytometric analysis revealed that OLI‐neu cells arrested in the G1 phase of the cell cycle underwent apoptosis in response to TGF‐β. TUNEL assays, apoptosis ELISA, and caspase assays substantiated the finding that OLI‐neu cells died after TGF‐β treatment. Cell death could be inhibited by application of pan‐caspase or caspase 8 and 9 inhibitors, whereas the inhibition of calpain was unaffected. Furthermore, we found a reduction of bcl‐X~L~ at the protein as well as at the mRNA level, while p27 was upregulated. The Smad cascade was activated while TGF‐β reduced the activity of the p42/p44 MAP kinase pathway. Together, these data show that TGF‐β induced apoptotic cell death in cells of oligodendroglial origin, whereby the signaling cascade involved the downregulation of antiapoptotic signaling such as bcl‐X~L~ leading to the activation of caspases. GLIA 40:95–108, 2002. © 2002 Wiley‐Liss, Inc.