GSTA4 mediates reduction of cisplatin ototoxicity in female mice

• DOI: 10.1038/s41467-019-12073-0
• Publication Date: 2019-09-12T10:02:34Z
• Authors: Hyo-Jin Park; Mi-Jung Kim; Christina Rothenb...; Ashok Kumar; Edith M. Sampson; Dalian Ding; Chul Han; Karessa White; Kevin Boyd; Senthilvelan Manohar; Yong-Hwan Kim; Maria S. Ticsa; Aaron S. Gomez; Isabela Caicedo; Upal Bose; Paul J. Linser; Takuya Miyakawa; Masaru Tanokura; Thomas C. Foster; Richard Salvi; Shinichi Someya
• Keywords: Ototoxicity

Cisplatin is one of the most widely used chemotherapeutic drugs for treatment cancer. Unfortunately, its major side effects permanent hearing loss. Here, we show that glutathione transferase α4 (GSTA4), a member Phase II detoxifying enzyme superfamily, mediates reduction cisplatin ototoxicity by removing 4-hydroxynonenal (4-HNE) in inner ears female mice. Under treatment, loss Gsta4 results more profound mice compared to male stimulates GSTA4 activity ear wild-type, but not wild-type In Gsta4-/- mice, increased levels 4-HNE cochlear neurons CBA/CaJ ovariectomy decreases mRNA expression Gsta4, and protein ears. Thus, our findings suggest GSTA4-dependent detoxification may play role estrogen-mediated neuroprotection.