首页> 美国卫生研究院文献>Scientific Reports >Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1/DAF-16 Signalling
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Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1/DAF-16 Signalling

机译:有机铀(II)配合物通过JNK-1 / DAF-16信号传导减轻秀丽隐杆线虫的氧化应激并阻止与年龄相关的恶化

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摘要

New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes >3 and >4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes >1–4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6-p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex >3 and >4 ameliorates the polyQ (a Huntington’s disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington’s disease models of C. elegans. From these observations, we hope that new Ru(ƞ6-p-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.
机译:合成了新的钌(II)配合物,并通过各种光谱分析技术对其进行了表征。 X射线晶体学证实了配合物> 3 和> 4 的结构。对该复合物进行了研究,研究了其抗氧化特性,并显示出比维生素C更高的体外DPPH自由基清除活性。我们发现,复合物> 1-4 赋予了对氧化应激的耐受性,并延长了平均寿命mev-1突变蠕虫和野生型秀丽隐杆线虫的鉴定。进一步的机理研究和报道基因表达分析表明,Ru(ƞ 6 -p-cymene)复合物维持细胞内的氧化还原状态,并通过激活JNK-1 / DAF-16信号轴并可能提供抗逆性。通过其他抗氧化剂反应途径。值得注意的是,复杂的> 3 和> 4 改善了在秀丽隐杆线虫的Huntington疾病模型中polyQ(与Huntington疾病相关的蛋白)介导的蛋白毒性和相关的行为缺陷。从这些观察结果,我们希望新的Ru(ƞ 6 -p-cymene)复合物可以进一步被认为是延缓衰老和与年龄有关的神经退行性疾病的潜在药物。

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