A Cell Death Cascade after Mechanical Injury
This week, Arundine et al. explore some of the underlying cellular mechanisms in an in vitro model of sublethal stretch injury.
Cultured neurons were grown on flexible membranes and then exposed to a 1 sec vacuum pulse that stretched cell processes by 130%.
The stretch did not kill the neurons but did make them more vulnerable to excitotoxic death mediated by low concentrations of NMDA.
Stretch caused DNA fragmentation, but the authors could find no evidence of caspase-dependent or -independent apoptosis.
Instead, the cells suffered mitochondrial dysfunction and produced excess reactive oxygen species (ROS). The ROS increased neuronal vulnerability by combining with nitric oxide (NO) to produce peroxynitrite, leading to protein nitration, DNA degradation, and cell death. NO was not the direct product of stretch but specifically required NMDA receptor-mediated signaling pathways.
Mark Arundine, Michelle Aarts, Anthony Lau, and Michael Tymianski
The Journal of Neuroscience (see pages 8106-8123)
Contact: Mary Anne Walker
mwalker@sfn.org
202-462-6688
Society for Neuroscience
O cascadã de celule moarte dupã Leziuni mecanice - A Cell Death Cascade after Mechanical Injury - articole medicale engleza - startsanatate