Light- and sodium azide-induced death of RGC-5 cells in culture occurs via different mechanisms |
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Authors: | Dan Ji Tengku A Kamalden Susana del Olmo-Aguado Neville N Osborne |
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Institution: | 1.Nuffield Laboratory of Ophthalmology, John Radcliffe Hospital,University of Oxford,Oxford,UK;2.Fundación de Investigación Oftalmológica,Instituto Oftalmológico Fernández-Vega,Oviedo,Spain;3.The First People’s Hospital of Changde,Changde,People’s Republic of China |
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Abstract: | Previous studies have shown that light impinging on the retina in situ has the capacity to kill neuronal and non-neuronal
cells in vitro by interacting directly with mitochondrial constituents. A number of fluorophores are associated with mitochondria
which can potentially absorb different wave-lengths of light, including cytochrome oxidase. The aim of the present study was
to compare the death mechanism of a light insult to RGC-5 cells in culture with that of sodium azide. Sodium azide’s main
toxic action is in inhibiting the function of cytochrome oxidase in the mitochondrial electron transport chain. Our studies
showed that light and sodium azide kill RGC-5 cells via different mechanisms although some similarities do occur. Both inducers
of cell death caused the generation of reactive oxygen species (ROS), the expression of phosphatidylserine, the breakdown
of DNA and the activation of p38 MAPK, resulting in its translocation from the nucleus to the cytoplasm. However, light-induced
cell death occurs via necroptosis, in that it was inhibited by necrostatin-1 and was caspase-independent. This was not the
case for sodium azide, where the death process was caspase-dependent, occurred via apoptosis and was unaffected by necrostatin-1.
Moreover, light caused an activation of the apoptosis inducing factor (AIF), c-Jun, JNK and HO-1, but it did not affect alpha
fodrin or caspase-3. In contrast, sodium azide caused the activation of alpha fodrin and the stimulation of caspase-3 content
without influencing AIF, c-Jun, JNK or HO-1. Therefore we conclude that light does not have a specific action on cytochrome
oxidase in mitochondria to cause cell death. |
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