Effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss in mice
| Autor: | Shinichi Someya, Kevin Boyd, Hyo-Jin Park, Dalian Ding, Chul Han, Richard Salvi, Karessa White, Mi-Jung Kim |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Aging Hearing loss Endogeny medicine.disease_cause Biochemistry Article GSTA4 Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Internal medicine Genetics medicine otorhinolaryngologic diseases Animals Molecular Biology Spiral ganglion Cochlea Glutathione Transferase Cell Biology Glutathione Presbycusis 030104 developmental biology medicine.anatomical_structure chemistry Mice Inbred CBA sense organs medicine.symptom Spiral Ganglion 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Exp Gerontol |
| ISSN: | 1873-6815 |
| Popis: | The glutathione transferase (GST) detoxification system converts exogenous and endogenous toxins into a less toxic form by conjugating the toxic compound to reduced glutathione (GSH) by a variety of GST enzymes. Of the ~20 GST isoforms, GSTA4 exhibits high catalytic efficiency toward 4-hydroxynonenal (4-HNE), one of the most abundant end products of lipid peroxidation that contributes to neurodegenerative diseases and age-related disorders. Conjugation to GSH by GSTA4 is thought to be a major route of 4-HNE elimination. In the current study, we investigated the effects of Gsta4 deficiency on age-related cochlear pathology and hearing loss using young (3–5 months old) and old (24–25 months old) Gsta4(+/+) and Gsta4(−/−) mice that were backcrossed onto the CBA/CaJ mouse strain, a well-established model of age-related hearing loss (AHL). At 3–5 months of age, loss of Gsta4 resulted in decreased total GSTA activity toward 4-HNE in the inner ears of young mice. However, there were no differences in the levels of 4-HNE in the inner ears between Gsta4(+/+) and Gsta4(−/−) mice at 3–5 or 24–25 months of age. No histological abnormalities were observed in the cochlea and no hearing impairments were observed in young Gsta4(−/−) mice. At 24–25 months of age, both Gsta4(+/+) and Gsta4(−/−) mice showed elevated ABR thresholds compared to 3-month-old mice, but there were no differences in ABR thresholds, cochlear spiral ganglion neuron densities, or stria vascularis thickness between Gsta4(+/+) and Gsta4(−/−) mice. Together, these results suggest that under normal physiological conditions or during normal aging, GSTA4 is not essential for removal of 4-HNE in mouse inner ears. |
| Databáze: | OpenAIRE |
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