Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1869, Issue 4, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2021.119204
Keywords
Cisplatin; Ototoxicity; XIAP; Organotypic culture; Hair cell
Categories
Funding
- National Natural Science Fundation of China [82071069]
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Cisplatin is an effective drug for solid tumors, but it often causes ototoxicity. This study found that overexpression of XIAP can protect cochlear hair cells from cisplatin-induced injury.
Cisplatin is a platinum-containing drug with ototoxicity commonly used clinically and has significant efficacy against a variety of solid tumors. One of the most important mechanisms of ototoxicity is that cisplatin induces apoptosis of hair cells. According to relevant literature, X-linked inhibitor of apoptosis protein (XIAP, antiapoptotic protein) could inhibit the apoptotic pathway. We hypothesized that this protein might protect cochlear hair cells from cisplatin-induced injury. To figure it out, we treated cochlea of normal mice with various concentrations of cisplatin to observe the response and morphology of hair cells and determine a reasonable concentration. Next, Western Blot and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) experiments were conducted to make an investigation about the expression of XIAP protein and mRNA. In addition, we constructed and identified XIAP overexpressing mice. Finally, we treated cochlear tissues of normal and over expressing mice with cisplatin to investigate the cyto-protection of XIAP on hair cells, respectively. It was found that 50 mu mol/L cisplatin resulted in significant loss and disorganization of hair cells, while simultaneously downregulating the protein and mRNA of XIAP. In XIAP overexpressing mice, the loss and disorganization of hair cells were significantly lessened. These results showed that XIAP can lessen cisplatin-induced hair cell loss and play a role in otoprotection.
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