Phenazine derivatives cause proteotoxicity and stress in C. elegans.
Phenazine derivatives cause proteotoxicity and stress in C. elegans.
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DOI：
10.1016/j.neulet.2014.09.055
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发表时间：
2015-01-01
影响因子：
2.5
通讯作者：
Caldwell KA
中科院分区：
文献类型：
--
作者：
Ray A;Rentas C;Caldwell GA;Caldwell KA
人们普遍认为细菌代谢物对动物系统有毒性作用。吩嗪类化合物是氧化还原活性外毒素类中常见的细菌代谢物。这些化合物已被证明对土壤无脊椎动物秀丽线虫具有毒性，能够引起氧化应激和致死。在这里，我们报告了三个不同的吩嗪分子(吩嗪-1-羧酸、绿青素和1-羟基吩嗪)的长期、低水平暴露在体内上调内质网应激反应和增强超氧化物歧化酶报告基因的表达。暴露在这些分子中也增加了线虫体壁肌肉细胞中的聚谷氨酰胺和α-突触核蛋白。蠕虫暴露于这些吩嗪后，表达野生型α-突触核蛋白的多巴胺神经元的敏感性增加，这表明可能存在蛋白质稳态的缺陷。添加抗氧化剂未能挽救这些化合物引起的神经毒性和蛋白质聚集表型。因此，在整个动物中，对这些吩嗪类药物的反应所产生的超氧阴离子自由基的增加似乎与观察到的毒性表型无关。总而言之，这些数据为进一步研究吩嗪类药物的神经退行性影响提供了理由。
It is widely recognized that bacterial metabolites have toxic effects in animal systems. Phenazines are a common bacterial metabolite within the redox-active exotoxin class. These compounds have been shown to be toxic to the soil invertebrate Caenorhabditis elegans with the capability of causing oxidative stress and lethality. Here we report that chronic, low-level exposure to three separate phenazine molecules (phenazine-1-carboxylic acid, pyocyanin and 1-hydroxyphenazine) upregulated ER stress response and enhanced expression of a superoxide dismutase reporter in vivo. Exposure to these molecules also increased of polyglutamine and α-synuclein in the bodywall muscle cells of C. elegans. Exposure of worms to these phenazines caused additional sensitivity in dopamine neurons expressing wild-type α-synuclein, indicating a possible defect in protein homeostasis. The addition of an anti-oxidant failed to rescue the neurotoxic and protein aggregation phenotypes caused by these compounds. Thus, increased production of superoxide radicals that occurs in whole animals in response to these phenazines appears independent from the toxicity phenotype observed. Collectively, these data provide cause for further consideration of the neurodegenerative impact of phenazines.
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DOI：
10.1073/pnas.042497999
发表时间：
2002-03-05
影响因子：
11.1
作者：
Nass, R;Hall, DH;Blakely, RD
通讯作者：
Blakely, RD
DOI：
10.1152/ajplung.00086.2003
发表时间：
2003-09-01
影响因子：
4.9
作者：
Denning, GM;Iyer, SS;Britigan, BE
通讯作者：
Britigan, BE
影响因子：
4
作者：
Haynes, Cole M.;Ron, David
通讯作者：
Ron, David
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
DOI：
10.1073/pnas.0711018105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Hamamichi, Shusei;Rivas, Renee N.;Caldwell, Guy A.
通讯作者：
Caldwell, Guy A.