Cisplatin induces damage of auditory cells: Possible relation with dynamic variation in calcium homeostasis and responding channels

The present study was aimed to explore the possible mechanism(s) underlying the action of cisplatin on auditory cells of mice in vitro, with special attention given to the dynamic variation in calcium homeostasis and responding channels. The apoptosis of auditory cells was tested by flow cytometry and TUNEL staining. The expressions of inositol 1,4,5-trisphosphate receptors (IP3R), voltage-dependent anion channel 1 (VDAC1), phosphorylated protein kinase R-like ER kinase (p-PERK), activating transcription factor 6 (ATF6), caspase-12, bcl-2, bax, cleaved caspase-9, cleaved caspase-3, beclin-1 and light chain 3β (LC3B) were measured by immunofluorescence or Western blotting. The calcium variations in subcellular structures were evaluated by Rhod-2 AM and Mag-Fluo-4 AM staining. The colocalization ratio between IP3R and beclin-1 was determined by immunocytochemistry. We found that cisplatin exposure induced the apoptosis of HEI-OC1 cells and hair cells (HCs) in a caspase-3 dependent manner. This apoptotic process was attributed to the activation of endoplasmic reticulum (ER) stress and mitochondrial pathway and, meanwhile, accompanied by variation in calcium homeostasis and responding channels. Interestingly, we also observed that IP3R might dissociate from beclin-1 to motivate autophagy under the cisplatin insult. Overall, the findings from this work indicate that cisplatin leads to auditory cell damage of mice in vitro, which is closely relevant to dynamic variation in calcium homeostasis and responding channels in subcellular structure. •Cisplatin induced ER stress through facilitating ER calcium efflux.•Cisplatin activated mitochondrial pathway by promoting mitochondrial calcium influx.•Cisplatin led to autophagy via eliciting the dissociation between IP3R and beclin-1.