GSTA4 mediates reduction of cisplatin ototoxicity in female mice.
Cisplatin is one of the most widely used chemotherapeutic drugs for the treatment of cancer. Unfortunately, one of its major side effects is permanent hearing loss. Here, we show that glutathione transferase α4 (GSTA4), a member of the Phase II detoxifying enzyme superfamily, mediates reduction of cisplatin ototoxicity by removing 4-hydroxynonenal (4-HNE) in the inner ears of female mice. Under cisplatin treatment, loss of Gsta4 results in more profound hearing loss in female mice compared to male mice. Cisplatin stimulates GSTA4 activity in the inner ear of female wild-type, but not male wild-type mice. In female Gsta4
Animals, Auditory Threshold, Capillaries, Cisplatin, Cochlea, Crosses, Genetic, DNA Damage, Evoked Potentials, Auditory, Brain Stem, Female, Gene Expression Regulation, Glutathione Transferase, Hearing Loss, Male, Mice, Inbred CBA, Ototoxicity, Oxidative Stress, RNA, Messenger, Spiral Ganglion
Medical Subject Headings
Animals; Auditory Threshold; Capillaries; Cisplatin; Cochlea; Crosses, Genetic; DNA Damage; Evoked Potentials, Auditory, Brain Stem; Female; Gene Expression Regulation; Glutathione Transferase; Hearing Loss; Male; Mice, Inbred CBA; Ototoxicity; Oxidative Stress; RNA, Messenger; Spiral Ganglion
Digital Object Identifier (DOI)
Park, Hyo-Jin; Kim, Mi-Jung; Rothenberger, Christina; Kumar, Ashok; Sampson, Edith M; Ding, Dalian; Han, Chul; White, Karessa; Boyd, Kevin; Manohar, Senthilvelan; Kim, Yong-Hwan; Ticsa, Maria S; Gomez, Aaron S; Caicedo, Isabela; Bose, Upal; Linser, Paul J; Miyakawa, Takuya; Tanokura, Masaru; Foster, Thomas C; Salvi, Richard; and Someya, Shinichi, "GSTA4 mediates reduction of cisplatin ototoxicity in female mice." (2019). Translational Neuroscience. 2230.