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N‐Acetyl cysteine (NAC) attenuates neuronal cell death in culture not solely by up regulating glutathione (GSH).
Author(s) -
ABDUL MAJID AS,
OSBORNE NN
Publication year - 2009
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2009.262.x
Subject(s) - glutathione , programmed cell death , buthionine sulfoximine , reactive oxygen species , acetylcysteine , superoxide dismutase , intracellular , apoptosis , oxidative stress , chemistry , microbiology and biotechnology , pharmacology , retinal ganglion cell , biochemistry , biology , antioxidant , retinal , enzyme
Purpose To show that NAC attenuates GB (glutamate/buthionine sulfoximine)‐induced death to retinal ganglion cells (RGC‐5 cells) in culture by a mechanism that does not solely involve GSH. Methods Transformed retinal ganglion (RGC‐5) cells grown in culture were exposed to an insult of GB for defined periods. NAC at different concentrations or vehicle was added to the cultures over 24 hours. Reactive oxygen species (ROS) generation was measured using a dye 20,70‐dihydroethidium. Cell death was measured by use of an MTT and resazurin‐assays and evidence for apoptosis was obtained with an APOPercentage™ procedure. Glutathione (GSH), catalase (CAT), gluthathione‐S‐transferase (GST) and superoxide dismutase (SOD) were also determined using a different fluorescent procedure. Results NAC dose‐dependently attenuated GB‐induced generation of ROS and death by a form of apoptosis to RGC‐5 cells in culture. NAC also independently stimulated the production of not only GSH but also GST, CAT and SOD. Moreover, NAC attenuated GB‐induced loss of intracellular GSH, CAT and GST. Conclusion NAC significantly blunts oxidative‐induced death to RGC‐5 cells induced by GB. Evidence is also provided to show that NAC increases intracellular GSH, GST, CAT and SOD levels. The neuroprotective action of NAC is therefore complex and is not solely caused by an action on GSH.