Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12073-0
Keywords
-
Categories
Funding
- National Institute of Health [R03 DC011840, R01 DC012552, R01 DC014437]
- National Institute on Deafness and Communication Disorders [RO1 AG037984]
- Claude D. Pepper Older Americans Independence Centers at the University of Florida from the National Institute of Health [P30 AG028740]
- Evelyn F. McKnight Brain Research Foundation
- Japan Society for the Promotion of Science (JSPS) [26253081, 23228003]
- National Institute on Aging
- Grants-in-Aid for Scientific Research [26253081] Funding Source: KAKEN
Ask authors/readers for more resources
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 alpha 4 (GSTA4), a member of the Phase II detoxifying enzyme super-family, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available