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重组荞麦硫氧还蛋白摄入通过上调秀丽隐杆线虫 hsf-1 延长寿命和提高应激抗性。

Recombinant buckwheat glutaredoxin intake increases lifespan and stress resistance via hsf-1 upregulation in Caenorhabditis elegans.

机构信息

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China; Department of oncology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan 030032, PR China.

College of Life Science, Shanxi University, Taiyuan 030006, PR China.

出版信息

Exp Gerontol. 2018 Apr;104:86-97. doi: 10.1016/j.exger.2018.01.028. Epub 2018 Feb 4.

Abstract

Glutaredoxin (Grx) is a polypeptide with low molecular weight, which has been extracted from buckwheat and has been suggested to have multiple functions revolving around oxidative stress responses and cell signaling. Here, we report the antioxidant activity of recombinant buckwheat Grx (rbGrx) to reduce aging effects in Caenorhabditis elegans (C. elegans) as well as the mechanism involved. Our results showed that rbGrx beneficially affected the health span of C. elegans, including pharyngeal-pumping rate, locomotion, and lipofuscin accumulation. Furthermore, stress assay showed that rbGrx could extend the lifespan under both oxidative and heat stress. Further studies indicated that the longevity-extending effects of rbGrx could be attributed to its in vitro and in vivo antioxidant activities. After treatment with rbGrx, SOD activity, CAT activity, GSH content, and GSH/GSSG ratio were increased, while MDA content was decreased, which led to low intracellular levels of reactive oxygen species in C. elegans. Moreover, rbGrx up-regulated hsf-1 mRNA level and could not expand the lifespan of the hsf-1 mutant C. elegans (sy441); however, this had no effect on the transcription of daf-16 and skn-1 and could expand the lifespan of both daf-16 and skn-1 mutants. These results suggested dependency of the rbGrx effect on the heat shock transcription factor (HSF-1) and independency on both DAF-16 and SKN-1. In summary, our results demonstrated the anti-aging activity of rbGrx, which increased resistance to cellular stress and improved the health span of C. elegans. These results are very important for the use of rbGrx in anti-aging research.

摘要

谷氧还蛋白(Grx)是一种低分子量的多肽,已从荞麦中提取出来,并被认为具有多种功能,包括围绕氧化应激反应和细胞信号转导。在这里,我们报告重组荞麦 Grx(rbGrx)的抗氧化活性,以减少 Caenorhabditis elegans(秀丽隐杆线虫)的衰老效应及其涉及的机制。我们的结果表明,rbGrx 有益地影响了秀丽隐杆线虫的健康寿命,包括咽部抽吸率、运动和脂褐素积累。此外,应激试验表明 rbGrx 可以延长氧化和热应激下的寿命。进一步的研究表明,rbGrx 的延长寿命效应归因于其体外和体内的抗氧化活性。在用 rbGrx 处理后,SOD 活性、CAT 活性、GSH 含量和 GSH/GSSG 比值增加,而 MDA 含量降低,导致秀丽隐杆线虫细胞内活性氧水平降低。此外,rbGrx 上调了 hsf-1 mRNA 水平,但不能延长 hsf-1 突变体秀丽隐杆线虫(sy441)的寿命;然而,这对 daf-16 和 skn-1 的转录没有影响,并能延长 daf-16 和 skn-1 突变体的寿命。这些结果表明 rbGrx 的作用依赖于热休克转录因子(HSF-1),而不依赖于 DAF-16 和 SKN-1。总之,我们的结果表明 rbGrx 具有抗衰老活性,它提高了细胞应激的抵抗力,并改善了秀丽隐杆线虫的健康寿命。这些结果对于 rbGrx 在抗衰老研究中的应用非常重要。

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