Comparison of rat liver and brain proteasomes for oxidative stress-induced inactivation: Influence of ageing and dietary restriction

Comparison of rat liver and brain proteasomes for oxidative stress-induced inactivation: Influence of ageing and dietary restriction
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DOI:
10.1080/10715760802534812
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发表时间:
2009-01-01
影响因子:
3.3
通讯作者:
Keller, Jeffrey N.
Keller, Jeffrey N.
中科院分区:
生物学3区
文献类型:
--
作者:
Dasuri, Kalavathi;Nguyen, Anhthao;Keller, Jeffrey N.

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本研究探讨了大脑和肝脏来源的蛋白酶体复合物,以阐明是否有不同的敏感性,从这些组织的蛋白酶体复合物进行灭活后暴露于氧化应激。然后,它研究了衰老和饮食限制(DR)对所观察到的蛋白酶体失活的影响。研究使用了基于过滤的方法,该方法允许富集蛋白酶体复合物,所需的组织少于传统色谱法。结果表明,与来自肝脏的蛋白酶体复合物相比,大脑具有低得多的总体蛋白酶体活性水平,并且表现出对过氧化氢介导的失活的敏感性增加。有趣的是,脑蛋白酶体复合物似乎没有增加对4-羟基壬烯醛(HNE)诱导的失活的敏感性。令人惊讶的是,老化和DR诱导氧化应激介导的蛋白酶体抑制的影响最小。这些结果表明,与肝脏相比,大脑不仅具有较低水平的蛋白酶体活性,而且在暴露于某些(但肯定不是全部)氧化应激源后更容易失活。这些数据还表明,在某些实验环境中,衰老和DR可能不会显著调节蛋白酶体对失活的抵抗力。
The present study examined brain and liver derived proteasome complexes to elucidate if there is a differential susceptibility in proteasome complexes from these tissues to undergo inactivation following exposure to oxidative stressors. It then examined the influence of ageing and dietary restriction (DR) on the observed proteasome inactivation. Studies used a filtration based methodology that allows for enrichment of proteasome complexes with less tissue than is required for traditional chromatography procedures. The results indicate that the brain has much lower levels of overall proteasome activity and exhibits increased sensitivity to hydrogen peroxide mediated inactivation as compared to proteasome complexes derived from the liver. Interestingly, the brain proteasome complexes did not appear to have increased susceptibility to 4-hydroxynonenal (HNE)-induced inactivation. Surprisingly, ageing and DR induced minimal effects on oxidative stress mediated proteasome inhibition. These results indicate that the brain not only has lower levels of proteasome activity compared to the liver, but is also more susceptible to inactivation following exposure to some (but certainly not all) oxidative stressors. This data also suggest that ageing and DR may not significantly modulate the resistance of the proteasome to inactivation in some experimental settings.