Supplementary Material for: Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Endoplasmic reticulum (ER) stress arises when excessive improperly
folded proteins accumulate in the ER lumen. When ER stress occurs, the
unfolded protein response (UPR) is subsequently activated to restore ER
proteostasis. However, severe ER stress leads to apoptosis. Recent
studies have suggested that cisplatin cytotoxicity may be related to ER
stress. The purpose of this study was to determine whether ER stress
participates in cochlear cell apoptosis in a cisplatin-induced
ototoxicity rat model and to also determine the possible relationship
between ER stress and hearing loss. Our results revealed that treatment
with cisplatin upregulated the expression of active caspase-12 in
cochlear cells, which is indicative of cisplatin-induced activation of
ER-specific apoptosis. Increased expression of C/EBP homologous protein
(CHOP) and cleaved caspase-9 suggested a close relationship between
severe ER stress and mitochondria-dependent apoptosis in the cochlear
cells of cisplatin-treated rats. In addition, we found that
tauroursodeoxycholic acid (TUDCA), a promoter of ER proteostasis, had a
protective effect on cisplatin-induced hearing loss. These results
demonstrate that ER stress is involved in the cisplatin-induced
apoptosis of cochlear cells in vivo.