Mitochondrial pathway is involved in hydrogen-peroxide-induced apoptotic cell death of oligodendrocytes.
Oligodendrocytes, the myelin-forming cells of the CNS, are specifically sensitive to oxidative stress and respond by the onset of programmed cell death (PCD). To further unravel the molecular events underlying their enhanced susceptibility, we have investigated whether mitochondrial damage occurs during oxidative stress-induced PCD in cultured rat brain oligodendrocytes. Mitochondria are considered as a central control point of apoptosis, and mitochondrial dysfunction has been linked to neurodegenerative disease. Upon a number of stimuli through the release of cytochrome c, they coordinate caspase activation, causing morphological and biochemical changes associated with PCD. Oxidative stress was exerted by the application of hydrogen peroxide. The data show that hydrogen peroxide-induced apoptosis in oligodendrocytes involves mitochondrial damage and cytochrome c release and is accompanied by the activation of the death-related caspases 3 and 9. Concomitantly, the activation and nuclear translocation of extracellular signal regulated kinases ERK1,2 are observed, which have been implicated to participate in the regulation of cell death and survival. DNA fragmentation could not be attenuated by the ERK1,2 inhibitor PD 98059, indicating that the ERK1,2- pathway in oligodendrocytes may be involved in the initial survival response after exposure to stressful stimuli.
Mronga
Thomas
T
Department of Biology, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
Stahnke
Thomas
T
Goldbaum
Olaf
O
Richter-Landsberg
Christiane
C
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D015984:Causality; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D016877:Oxidants; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases