Triethyltin-induced stress responses and apoptotic cell death in cultured oligodendrocytes.
Triethyltin (TET)-induced neurotoxicity in the brain causes the formation of myelin edema and loss. Myelin deficits produced by early postnatal exposure to TET are permanent and cannot be repaired as the brain matures. The underlying causes have not been resolved. To investigate whether TET directly affects oligodendrocytes, the myelin-forming cells of the central nervous system, cultured rat brain oligodendrocytes were prepared and treated with TET. The data show that TET was cytotoxic for oligodendrocytes and led to the onset of programmed cell death, as indicated by DNA fragmentation. Cellular membranous extensions were severely damaged, and the nuclei appeared to be condensed and fragmented. Concomitantly, the small heat shock protein HSP32, also known as heme oxygenase-1 (HO-1), and an indicator of oxidative stress, as well as the activation of extracellular signal-regulated kinases 1 and 2 (ERK1,2), were observed. ERK1,2 have been implicated to participate in the regulation of cell death and survival. Myelin-specific proteins MBP and CNP were not affected. In TET-treated cells mitochondria redistributed from the processes to the cell somata near the nucleus, possibly as a consequence of microtubule disorganization. A disturbance of the mitochondrial membrane potential and mitochondrial fragmentation occurred. Hence, it might be hypothesized that oligodendroglial PCD, rather than axonal degeneration, contributes to myelin damage and deficits observed in rats after treatment with TET in vivo.
Stahnke
Thomas
T
Department of Biology, Molecular Biology, University of Oldenburg, Oldenburg, Germany.
Richter-Landsberg
Christiane
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014267:Triethyltin Compounds / Q000633:toxicity*
D014267:Triethyltin Compounds; C031575:triethyltin