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GSTA4 mediates reduction of cisplatin ototoxicity in female mice

Author

Listed:
  • Hyo-Jin Park

    (University of Florida)

  • Mi-Jung Kim

    (University of Florida)

  • Christina Rothenberger

    (University of Florida)

  • Ashok Kumar

    (University of Florida)

  • Edith M. Sampson

    (University of Florida)

  • Dalian Ding

    (State University of New York at Buffalo)

  • Chul Han

    (University of Florida)

  • Karessa White

    (University of Florida)

  • Kevin Boyd

    (University of Florida)

  • Senthilvelan Manohar

    (State University of New York at Buffalo)

  • Yong-Hwan Kim

    (Barrow Neurological Institute)

  • Maria S. Ticsa

    (University of Florida)

  • Aaron S. Gomez

    (University of Florida)

  • Isabela Caicedo

    (University of Florida)

  • Upal Bose

    (University of Florida)

  • Paul J. Linser

    (University of Florida)

  • Takuya Miyakawa

    (University of Tokyo)

  • Masaru Tanokura

    (University of Tokyo)

  • Thomas C. Foster

    (University of Florida)

  • Richard Salvi

    (State University of New York at Buffalo
    Asia University)

  • Shinichi Someya

    (University of Florida)

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−/− 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.

Suggested Citation

  • Hyo-Jin Park & Mi-Jung Kim & Christina Rothenberger & Ashok Kumar & Edith M. Sampson & Dalian Ding & Chul Han & Karessa White & Kevin Boyd & Senthilvelan Manohar & Yong-Hwan Kim & Maria S. Ticsa & Aar, 2019. "GSTA4 mediates reduction of cisplatin ototoxicity in female mice," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12073-0
    DOI: 10.1038/s41467-019-12073-0
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    Cited by:

    1. Hong-Tao Li & Liya Xu & Daniel J. Weisenberger & Meng Li & Wanding Zhou & Chen-Ching Peng & Kevin Stachelek & David Cobrinik & Gangning Liang & Jesse L. Berry, 2022. "Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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