Thioredoxin 2 (TXN2) is a small redox protein found in nearly all organisms. As a mitochondrial member of the thioredoxin antioxidant defense system, TXN2 interacts with peroxiredoxin 3 (PRDX3) to remove hydrogen peroxide. Accordingly, TXN2 is thought to play an important role in maintaining the appropriate mitochondrial redox environment and protecting the mitochondrial components against oxidative stress. In the current study, we investigated the effects of Txn2 haplodeficiency on cochlear antioxidant defenses, auditory function, and cochlear cell loss across the lifespan in wild-type (WT) and Txn2 heterozygous knockout (Txn2^+/−) mice backcrossed onto CBA/CaJ mice, a well-established model of age-related hearing loss. Txn2^+/− mice displayed a 58% decrease in TXN2 protein levels in the mitochondria of the inner ears compared to WT mice. However, Txn2 haplodeficiency did not affect the thioredoxin or glutathione antioxidant defense in both the mitochondria and cytosol of the inner ears of young mice. There were no differences in the levels of mitochondrial biogenesis markers, mitochondrial DNA content, or oxidative DNA and protein damage markers in the inner ears between young WT and Txn2^+/− mice. In a mouse inner ear cell line, knockdown of Txn2 did not affect cell viability under hydrogen peroxide treatment. Consistent with the tissue and cell line results, there were no differences in hair cell loss or spiral ganglion neuron density between WT and Txn2^+/− mice at 3–5 or 23–25 months of age. Furthermore, Txn2 haplodeficiency did not affect auditory brainstem response threshold, wave I latency, or wave I amplitude at 3–5, 15–16, or 23–25 months of age. Therefore, Txn2 haplodeficiency does not affect cochlear antioxidant defenses, accelerate degeneration of cochlear cells, or affect auditory function in mice across the lifespan.

硫氧还蛋白 2 (TXN2) 是一种小的氧化还原蛋白，几乎存在于所有生物体中。作为硫氧还蛋白抗氧化防御系统的线粒体成员，TXN2 与过氧还蛋白 3 (PRDX3) 相互作用以去除过氧化氢。因此，TXN2 被认为在维持适当的线粒体氧化还原环境和保护线粒体成分免受氧化应激方面发挥重要作用。在目前的研究中，我们研究了回交到CBA/CaJ 上的野生型 (WT) 和Txn2杂合敲除 ( Txn2 ^+/- ) 小鼠在整个生命周期中Txn2 单倍体缺陷对耳蜗抗氧化防御、听觉功能和耳蜗细胞损失的影响小鼠，一种成熟的与年龄相关的听力损失模型。TXN2与 WT 小鼠相比，^+/-小鼠内耳线粒体中的 TXN2 蛋白水平降低了 58%。然而，Txn2 单倍体缺陷不影响幼鼠内耳线粒体和细胞质中的硫氧还蛋白或谷胱甘肽抗氧化防御。年轻 WT 和Txn2 ^+/-小鼠的内耳中线粒体生物发生标记物、线粒体 DNA 含量或氧化 DNA 和蛋白质损伤标记物的水平没有差异。在小鼠内耳细胞系中，在过氧化氢处理下，敲低Txn2不影响细胞活力。与组织和细胞系结果一致，WT 和 WT 之间的毛细胞丢失或螺旋神经节神经元密度没有差异3-5 或 23-25 个月大的Txn2 ^+/-小鼠。此外，Txn2 单倍体缺陷不影响 3-5、15-16 或 23-25 个月大的听觉脑干反应阈值、I 波潜伏期或 I 波振幅。因此，Txn2 单倍体缺陷不会影响耳蜗抗氧化防御，加速耳蜗细胞的退化，或影响小鼠整个生命周期的听觉功能。