Regulating proteasome activity is a potent therapeutic aspect of age-related hearing loss, which has been proven to protect neurons from age-related damaging. PSMD11, subunit of the 19S proteasome regulatory particle, is known to mainly up-regulate proteasome activity and prolong aging. However, the mechanism of PSMD11 in age-related hearing loss has not been deeply explored. In the present study, we explore the function and mechanism of PSMD11 protecting neurons in d-Galactose (D-Gal) mimetic aging models. Age-related pathologies were detected by Taq-PCR, ABR, Transmission electron microscopy, toluidine blue and β-galactosidase staining. The relative expressions of the proteins were explored by Western blotting, oxyblot, immunoprecipitation and immunofluorescence. Flow cytometry was used to manifest the oxidative state. We discovered that proteasome activity was impaired with aging, and that ROS and toxic protein accumulated in D-Gal induced aging models. PSMD11 changed with aging, and was associated with the metabolism of proteasome activity in the D-Gal treated models. Moreover, the knockdown or overexpression of PSMD11 was sufficient to change the oxidative state caused by D-Gal. Our results also demonstrated that PSMD11 could bond to AMPKα1/2 in the auditory cortex and PC12 cells, and AMPKα2 but not AMPKα1 was efficient to regulate the function of PSMD11. Deeper insights into the mechanisms of regulating PSMD11 for the anti-aging process are needed, and may offer novel therapeutic methods for central presbycusis.

调节蛋白酶体的活性是与年龄有关的听力损失的有效治疗方面，已被证明可以保护神经元免受与年龄有关的损害。PSMD11是19S蛋白酶体调控颗粒的亚基，已知主要上调蛋白酶体活性并延长衰老。然而，PSMD11在与年龄有关的听力损失中的机制尚未得到深入研究。在本研究中，我们探讨的PSMD11保护神经元的功能和机制d-半乳糖（D-Gal）模拟衰老模型。通过Taq-PCR，ABR，透射电镜，甲苯胺蓝和β-半乳糖苷酶染色检测与年龄有关的病理。通过Western印迹，oxyblot，免疫沉淀和免疫荧光探索蛋白质的相对表达。流式细胞仪用于显示氧化状态。我们发现蛋白酶体活性会随着衰老而受损，并且ROS和有毒蛋白在D-Gal诱导的衰老模型中积累。PSMD11随着年龄的变化而变化，并与D-Gal处理的模型中的蛋白酶体活性代谢有关。而且，PSMD11的敲低或过表达足以改变D-Gal引起的氧化态。我们的研究结果还表明PSMD11可以与听觉皮层和PC12细胞中的AMPKα1/ 2结合，AMPKα2而非AMPKα1可以有效调节PSMD11的功能。需要对调节PSMD11的抗衰老过程的机制有更深入的了解，并可能为中枢性老花眼病提供新颖的治疗方法。