Ubiquitin and ubiquitin-conjugated protein expression in the rat cerebral cortex and hippocampus following traumatic brain injury (TBI)

Ubiquitin and ubiquitin-conjugated protein expression in the rat cerebral cortex and hippocampus following traumatic brain injury (TBI)
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DOI:
10.1016/j.brainres.2007.08.076
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发表时间:
2007-11
期刊:
影响因子:
2.9
通讯作者:
X. Yao;Jiong Liu;J. McCabe
X. Yao;Jiong Liu;J. McCabe
中科院分区:
医学3区
文献类型:
--
作者:
X. Yao;Jiong Liu;J. McCabe

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蛋白质周转的调节对真核细胞的存活至关重要。这一重要的细胞过程部分地由泛素-蛋白酶体系统通过泛素链与蛋白酶体降解的靶蛋白缀合而进行翻译后修饰来调节。本研究检测了持续创伤性脑损伤(TBI)大鼠CNS中泛素mRNA和蛋白的表达。实时荧光定量PCR结果显示,脑外伤后第1天,同侧大脑皮层ubA 52、ubB和ubC的mRNA水平显著降低,第3天,ubC的mRNA水平也显著低于对照组,但到第7天,ubA 52、ubB和ubC的mRNA水平均恢复到对照组水平。在同侧海马中,ubA 52 mRNA水平在TBI后第1-7天显著降低,而ubB和ubC mRNA水平仅在TBI后第1天降低。Western blotting发现,在TBI后第1-7天,同侧大脑皮层和海马中的游离泛素蛋白水平显著降低,而在TBI后第7天,同侧大脑皮层和海马中的泛素缀合蛋白在TBI后第3-7天显著增加。我们的研究表明,改变泛素系统功能的中枢神经系统有助于创伤性脑损伤的病理结果。
Regulation of protein turnover is essential to the survival of eukaryotic cells. This important cellular process is partly regulated by the ubiquitin–proteasome system through posttranslational modification by the conjugation of ubiquitin chains to proteins targeted for degradation by proteasomes. The present study examined ubiquitin mRNA and protein expression in the CNS of rats that sustained traumatic brain injury (TBI). Quantitative real-time polymerase chain reaction results indicated that mRNA levels of ubA52, ubB and ubC in the ipsilateral cerebral cortex were significantly decreased on Day 1 post-TBI, that ubC mRNA levels also were significantly lower than control on Day 3 post-TBI, but that by Day 7 post-TBI, ubA52, ubB and ubC mRNA levels had all returned to control levels. In the ipsilateral hippocampus, ubA52 mRNA levels were significantly lower on Days 1–7 post-TBI, while ubB and ubC mRNA levels were less only on Day 1 post-TBI. Western blotting found that free ubiquitin protein levels were significantly reduced in both ipsilateral cerebral cortex and hippocampus on Days 1–7 post-TBI, while there was markedly increased ubiquitin-conjugated protein in ipsilateral cerebral cortex on Day 7 and in hippocampus on Days 3–7 post-TBI. Our study suggests that altered ubiquitin system function in the CNS contributes to the pathological outcomes of TBI.