GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea: Possible role of the thioredoxin system as a functional backup for GSR

• DOI: 10.1371/journal.pone.0180817
• Publication Date: 2017-07-07T17:47:49Z
• Authors: Chul Han; Mi-Jung Kim; Dalian Ding; Hyo-Jin Park; Karessa White; Logan Walker; Tongjun Gu; Masaru Tanokura; Tatsuya Yamasoba; Paul Linser; Richard Salvi; Shinichi Someya
• Keywords: Glutathione reductase; Glutathione disulfide

Glutathione reductase (GSR), a key member of the glutathione antioxidant defense system, converts oxidized (GSSG) to reduced (GSH) and maintains intracellular redox state protect cells from oxidative damage. Previous reports have shown that Gsr deficiency results in defects host against bacterial infection, while diquat induces renal injury hypomorphic mice. In flies, overexpression GSR extended lifespan under hyperoxia. current study, we investigated roles cochlear using homozygous knockout mice were backcrossed onto CBA/CaJ mouse strain, normal-hearing strain does not carry specific Cdh23 mutation causes progressive hair cell degeneration early onset hearing loss. Gsr-/- displayed significant decrease activity GSH/GSSG ratios cytosol inner ears. However, did affect ABR (auditory brainstem response) thresholds, wave I amplitudes or latencies young No histological abnormalities observed cochlea Furthermore, there no differences activities cytosolic glutathione-related enzymes, including peroxidase glutamate-cysteine ligase, levels damage markers ears between WT contrast, resulted increased thioredoxin Therefore, normal physiological conditions, is essential for maintenance defenses cochlea. Given system known reduce GSSG GSH multiple species, our findings suggest can support reduction peripheral auditory system.