Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, 32611, USA.
Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, 32611, USA.
Hear Res. 2021 Mar 15;402:108002. doi: 10.1016/j.heares.2020.108002. Epub 2020 May 28.
Age-related hearing loss (AHL) is the most common form of hearing impairment. AHL is thought to be a multifactorial condition resulting from the interaction of numerous causes including aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. Cells possess many detoxification enzymes capable of removing thousands of cytotoxic xenobiotics and endogenous toxins such as 4-hydroxynonenal (4-HNE), one of the most abundant cytotoxic end products of lipid peroxidation. The cellular detoxification system involves three phases of enzymatic detoxification. Of these, the glutathione transferase (GST) detoxification system converts a toxic compound into a less toxic form by conjugating the toxic compound to reduced glutathione by GST enzymes. In this review, we describe the current understanding of the cochlear detoxification system and examine the growing link between GST detoxification, oxidative lipid damage, ototoxicity, and cochlear aging with a particular focus on the alpha-class GSTs (GSTAs). We also describe how exposure to ototoxic drugs, exposure to noise, or aging results in increased 4-HNE levels, how 4-HNE damages various cell components under stress conditions, and how GSTAs detoxify 4-HNE in the auditory system.
年龄相关性听力损失（AHL）是最常见的听力障碍形式。AHL 被认为是一种多因素疾病，是由许多原因相互作用引起的，包括衰老、遗传、噪声暴露以及内源性和外源性毒素暴露。细胞拥有许多解毒酶，能够清除数千种细胞毒性异源物和内源性毒素，如 4-羟基壬烯醛（4-HNE），这是脂质过氧化的最丰富的细胞毒性终产物之一。细胞解毒系统涉及三个酶促解毒阶段。在这些阶段中，谷胱甘肽转移酶（GST）解毒系统通过 GST 酶将有毒化合物与还原型谷胱甘肽结合，将有毒化合物转化为毒性较小的形式。在这篇综述中，我们描述了耳蜗解毒系统的当前认识，并研究了 GST 解毒、氧化脂质损伤、耳毒性和耳蜗老化之间日益增长的联系，特别关注 α 类 GSTs（GSTAs）。我们还描述了耳毒性药物暴露、噪声暴露或衰老如何导致 4-HNE 水平升高，4-HNE 在应激条件下如何损伤各种细胞成分，以及 GSTAs 如何在听觉系统中解毒 4-HNE。
