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- Title
Suramin Induces and Enhances Apoptosis in a Model of Hyperoxia-induced Oligodendrocyte Injury.
- Authors
Stark, Simone; Schüller, Alexandra; Sifringer, Marco; Gerstner, Bettina; Brehmer, Felix; Weber, Sven; Altmann, Rodica; Obladen, Michael; Bührer, Christoph; Felderhoff-Mueser, Ursula
- Abstract
Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 µM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin led to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.
- Subjects
SURAMIN; APOPTOSIS; OXIDATIVE stress; IMMUNOBLOTTING; GENE expression
- Publication
Neurotoxicity Research, 2008, Vol 13, Issue 3/4, p197
- ISSN
1029-8428
- Publication type
Article
- DOI
10.1007/BF03033503