Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion Neurons In Vitro

Figure 6

Major apoptotic pathways in SGNs induced by oubain treatment. Genes that respond to intrinsic stimulation are believed to be involved in the mitochondrial pathway, and two major factors appear to be important, namely cytochrome C and apoptosis inducing factor (AIF). The pathway began with Caspase-9 activation, which was followed by executioner Caspases that resulted in proteolytic activity and nuclear damage (DNA fragmentation). The extrinsic pathway-responding genes were triggered first by cell-surface occupation of receptors belonging to the TNF/TNF R superfamily, which activate Fas causing the recruitment of Fas-associated protein with death domain (FADD). Then, Caspase-8 cleaves other pro-Caspases, which effectively initiates a Caspase cascade that ultimately drives apoptosis. Caspase-8 activation can also activate Bak, Bid, and Bax, which enhance mitochondrial damage and promote leakage of cytochrome C. Since many groups of genes are involved in the intrinsic and extrinsic pathways, many of which belong to the p53 superfamily, it was inevitable that the p53 signaling pathway was involved in ouabain-induced apoptosis.