GSTA4 mediates reduction of cisplatin ototoxicity in female mice
| العنوان: | GSTA4 mediates reduction of cisplatin ototoxicity in female mice |
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| المؤلفون: | Aaron S. Gomez, Yong Hwan Kim, Thomas C. Foster, Mi-Jung Kim, Christina Rothenberger, Upal Bose, Richard Salvi, Isabela Caicedo, Karessa White, Senthilvelan Manohar, Hyo-Jin Park, Dalian Ding, Masaru Tanokura, Edith M. Sampson, Maria S. Ticsa, Paul J. Linser, Ashok V. Kumar, Shinichi Someya, Takuya Miyakawa, Chul Han, Kevin Boyd |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, medicine.medical_treatment, General Physics and Astronomy, 0302 clinical medicine, lcsh:Science, Cancer genetics, Glutathione Transferase, Cancer, Multidisciplinary, 3. Good health, Cochlea, medicine.anatomical_structure, Toxicity, Auditory system, Female, medicine.symptom, Spiral Ganglion, medicine.drug, medicine.medical_specialty, Hearing loss, Science, Neuroprotection, General Biochemistry, Genetics and Molecular Biology, Article, GSTA4, 03 medical and health sciences, Ototoxicity, Internal medicine, medicine, Evoked Potentials, Auditory, Brain Stem, otorhinolaryngologic diseases, Animals, Inner ear, RNA, Messenger, Hearing Loss, Crosses, Genetic, Cisplatin, Chemotherapy, business.industry, Auditory Threshold, General Chemistry, medicine.disease, Capillaries, Oxidative Stress, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Mice, Inbred CBA, lcsh:Q, sense organs, business, 030217 neurology & neurosurgery, DNA Damage, Neuroscience |
| الوصف: | 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. A common complication of cisplatin-based chemotherapy is hearing loss. Here, Park et al. show that glutathione transferase α4 (GSTA4) contributes to reducing cisplatin toxicity in the inner ear of female mice by removing 4-hydroxynonenal (4-HNE). |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef455fed7880214a94ab611dd2d6b78d http://link.springer.com/article/10.1038/s41467-019-12073-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ef455fed7880214a94ab611dd2d6b78d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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