Ding Qunxing, Reinacker Kristi, Dimayuga Edgardo, Nukala Vidya, Drake Jennifer, Butterfield D Allan, Dunn Jay C, Martin Sarah, Bruce-Keller Annadora J, Keller Jeffrey N
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
FEBS Lett. 2003 Jul 10;546(2-3):228-32. doi: 10.1016/s0014-5793(03)00582-9.
Numerous studies suggest that proteasome inhibition may play a causal role in mediating the increased levels of protein oxidation and neuron death observed in conditions associated with oxidative stress. In the present study we demonstrate that administration of non-toxic levels of oxidative stress does not result in impairment of 20S/26S proteasome activity, and actually increases the expression of specific proteasome subunits. Non-toxic levels of oxidative stress were observed to elevate the amount of protein oxidation in the presence of preserved proteasomal function, suggesting that proteasome inhibition may not mediate increases in protein oxidation following low-level oxidative stress. Preserving basal proteasome function appears to be critical to preventing the neurotoxicity of low-level oxidative stress, based on the ability of proteasome inhibitor treatment to exacerbate oxidative stress toxicity. Taken together, these data indicate that maintaining neural proteasome function may be critical to preventing neurotoxicity, but not the increase in protein oxidation, following low-level oxidative stress.
众多研究表明，蛋白酶体抑制可能在介导与氧化应激相关的条件下所观察到的蛋白质氧化水平升高和神经元死亡中起因果作用。在本研究中，我们证明给予无毒水平的氧化应激不会导致20S/26S蛋白酶体活性受损，实际上还会增加特定蛋白酶体亚基的表达。在蛋白酶体功能得以保留的情况下，观察到无毒水平的氧化应激会提高蛋白质氧化量，这表明蛋白酶体抑制可能不会介导低水平氧化应激后蛋白质氧化的增加。基于蛋白酶体抑制剂治疗加剧氧化应激毒性的能力，维持基础蛋白酶体功能似乎对于预防低水平氧化应激的神经毒性至关重要。综上所述，这些数据表明，维持神经蛋白酶体功能对于预防低水平氧化应激后的神经毒性可能至关重要，但对于蛋白质氧化的增加并非如此。
