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Publication : Overexpression of XIAP inhibits cisplatin-induced hair cell loss.

First Author  Li Y Year  2022
Journal  Biochim Biophys Acta Mol Cell Res Volume  1869
Issue  4 Pages  119204
PubMed ID  35026350 Mgi Jnum  J:322618
Mgi Id  MGI:6867637 Doi  10.1016/j.bbamcr.2021.119204
Citation  Li Y, et al. (2022) Overexpression of XIAP inhibits cisplatin-induced hair cell loss. Biochim Biophys Acta Mol Cell Res 1869(4):119204
abstractText  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, anti-apoptotic 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 overexpressing mice with cisplatin to investigate the cyto-protection of XIAP on hair cells, respectively. It was found that 50 mumol/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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