Liu Jen-Jane, Zhao Heng, Sung Jae-Hoon, Sun Guo-Hua, Steinberg Gary K
Department of Neurosurgery and Stanford Stroke Center, Stanford University, Stanford, California 94305-5487, USA.
Neuroreport. 2006 Nov 6;17(16):1691-5. doi: 10.1097/01.wnr.0000236868.83970.79.
Dysfunction of the ubiquitin-proteasome system has recently been linked to stroke. Ischemia may cause increased protein misfolding and inhibit the proteasome, shifting the balance from free ubiquitin to conjugated ubiquitin. In this study, we examine the effect of hypothermia on the distribution of total and free ubiquitin, as well as the levels of conjugated ubiquitin after experimental stroke using a focal cerebral ischemia model. We show that hypothermia prevents redistribution of ubiquitin following ischemia, largely through preservation of intracellular cytoplasmic free ubiquitin. We also show that hypothermia blocks the increase in conjugated ubiquitin observed after stroke. Our data indicate that hypothermia's neuroprotection is mediated, in part, through preservation of ubiquitin-proteasome system function.
泛素-蛋白酶体系统功能障碍最近被认为与中风有关。缺血可能导致蛋白质错误折叠增加并抑制蛋白酶体，使平衡从游离泛素转向结合泛素。在本研究中，我们使用局灶性脑缺血模型，研究了低温对实验性中风后总泛素和游离泛素分布以及结合泛素水平的影响。我们发现，低温可防止缺血后泛素的重新分布，主要是通过保留细胞内细胞质游离泛素实现的。我们还发现，低温可阻止中风后观察到的结合泛素增加。我们的数据表明，低温的神经保护作用部分是通过保留泛素-蛋白酶体系统功能来介导的。
