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Publication : GSTA4 mediates reduction of cisplatin ototoxicity in female mice.

First Author  Park HJ Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  4150
PubMed ID  31515474 Mgi Jnum  J:279409
Mgi Id  MGI:6362367 Doi  10.1038/s41467-019-12073-0
Citation  Park HJ, et al. (2019) GSTA4 mediates reduction of cisplatin ototoxicity in female mice. Nat Commun 10(1):4150
abstractText  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 alpha4 (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(-/-) mice, cisplatin treatment results in increased levels of 4-HNE in cochlear neurons compared to male Gsta4(-/-) mice. In CBA/CaJ mice, ovariectomy decreases mRNA expression of Gsta4, and the levels of GSTA4 protein in the inner ears. Thus, our findings suggest that GSTA4-dependent detoxification may play a role in estrogen-mediated neuroprotection.
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