title: TGF-beta induces cell death in the oligodendroglial cell line OLI-neu.
abstract: We have shown that TGF-beta plays an important role during the period of developmental cell death in the nervous system. Immunoneutralization of TGF-beta 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-beta 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-beta. TUNEL assays, apoptosis ELISA, and caspase assays substantiated the finding that OLI-neu cells died after TGF-beta 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-beta reduced the activity of the p42/p44 MAP kinase pathway. Together, these data show that TGF-beta 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.
authors.affiliation: Department of Anatomy and Cell Biology, Medical Faculty, University of Saarland, Homburg/Saar, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuster
authors.forename: Herdis
authors.initials: H
authors.lastname: Bender
authors.forename: Anja
authors.initials: A
authors.lastname: Philippi
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Jens
authors.initials: J
authors.lastname: Strelau
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020287:In Situ Nick-End Labeling; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D002154:Calpain; D053148:Caspase 3; D020169:Caspases