GSTA4 mediates reduction of cisplatin ototoxicity in female mice.

Document Type

Article

Abstract

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

Keywords

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

Publication Date

9-12-2019

Publication Title

Nat Commun

ISSN

2041-1723

Volume

10

Issue

1

First Page

4150

Last Page

4150

PubMed ID

31515474

Digital Object Identifier (DOI)

10.1038/s41467-019-12073-0

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