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Shun-Ping Huang, Shu-Fung Lin, Rong-Kung Tsai; Ethambutol-induced autophagy deregulation and cytotoxic effects in retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1812.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the mechanism of cytotoxic effects of ethambutol in retinal ganglion cells
Cultured retinal ganglion cells (RGC-5) were exposed to 2 to 12 M ethambutol (EMB) and cell viability was quantified by MTS assay. Autophagy was studied in RGC-5 cells staining with LC3b,beclin-1 and p62. Lysosomes in cells were stained with Lysotracker and LAMP-1.
Following exposure to EMB, RGC-5 cells developed cytosolic vacuoles within 1 h and underwent cell lysis within 24 h. The levels of LC3-II, beclin-1 and p62, as well as the number autophagic vacuoles (AVs), increased following EMB treatment, indicating that autophagy was activated. Protein kinase C-delta inhibitor, rottlerin, protected RGC-5 cells from EMB-induced cytoplasmic vacuoles formation and cell death. Rottlerin attenuated EMB-induced caspase 3 activation in RGC-5 cells.
EMB induced vacuole formation and cell death in RGC-5 cells. Initially, vacuoles developed from enlarged lysosomes, followed by activation the autophagy pathway and formation of LC-3 positive AVs. EMB-induced cytotoxic effects in RGC-5 cells are intimately correlated and regulated by the PKC delta signal pathway.
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