Xanthine Dehydrogenase Is a Modulator of Dopaminergic Neurodegeneration in Response to Bacterial Metabolite Exposure in C. elegans.
Xanthine Dehydrogenase Is a Modulator of Dopaminergic Neurodegeneration in Response to Bacterial Metabolite Exposure in C. elegans.
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黄嘌呤脱氢酶是C.优雅
DOI：
10.3390/cells12081170
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发表时间：
2023-04-15
期刊：
影响因子：
6
通讯作者：
Caldwell, Kim A.
中科院分区：
文献类型：
--
作者：
Thies, Jennifer L.;Willicott, Karolina;Craig, Maici L.;Greene, Madeline R.;DuGay, Cassandra N.;Caldwell, Guy A.;Caldwell, Kim A.
氧化应激是帕金森氏病(PD)的一个促成因素。考虑到散发性帕金森病的流行，环境暴露被认为会增加活性氧，并刺激或加剧神经退行性变。我们先前已经确定，暴露于土壤中常见的细菌--维尼链霉菌(Streptomyces venezuelae，S.ven)，会增加秀丽隐杆线虫的氧化应激和线粒体功能障碍，导致多巴胺(DA)能神经变性。在这里，在线虫体内暴露S.ven代谢物之后进行了RNA-Seq分析。在差异识别的基因中，有一半与转录因子DAF-16(FOXO)相关，该转录因子是调节胁迫反应的关键节点。我们的DEGS富含第一阶段(CYP)和第二阶段(UGT)解毒基因，以及与氧化代谢相关的非CYP第一阶段酶，包括下调的黄嘌呤脱氢酶基因XDH-1。在钙的作用下，XDH-1酶表现出可逆的相互转化为黄嘌呤氧化酶(XO)。美国VEN代谢物暴露可提高线虫体内XO活性。钙的络合作用减少了XDH-1向XO的转化，并对S.ven暴露产生神经保护作用，而补充CaCl2则增强了神经退行性变。这些结果提示了一种防御机制，即划定可用于相互转化为XO的XDH-1池，以及相关的ROS产生，以响应代谢物暴露。
Oxidative stress is a contributing factor to Parkinson’s disease (PD). Considering the prevalence of sporadic PD, environmental exposures are postulated to increase reactive oxygen species and either incite or exacerbate neurodegeneration. We previously determined that exposure to the common soil bacterium, Streptomyces venezuelae (S. ven), enhanced oxidative stress and mitochondrial dysfunction in Caenorhabditis elegans, leading to dopaminergic (DA) neurodegeneration. Here, S. ven metabolite exposure in C. elegans was followed by RNA-Seq analysis. Half of the differentially identified genes (DEGs) were associated with the transcription factor DAF-16 (FOXO), which is a key node in regulating stress response. Our DEGs were enriched for Phase I (CYP) and Phase II (UGT) detoxification genes and non-CYP Phase I enzymes associated with oxidative metabolism, including the downregulated xanthine dehydrogenase gene, xdh-1. The XDH-1 enzyme exhibits reversible interconversion to xanthine oxidase (XO) in response to calcium. S. ven metabolite exposure enhanced XO activity in C. elegans. The chelation of calcium diminishes the conversion of XDH-1 to XO and results in neuroprotection from S. ven exposure, whereas CaCl2 supplementation enhanced neurodegeneration. These results suggest a defense mechanism that delimits the pool of XDH-1 available for interconversion to XO, and associated ROS production, in response to metabolite exposure.
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影响因子：
4.1
作者：
Caldwell KA;Thies JL;Caldwell GA
通讯作者：
Caldwell GA
影响因子：
3.6
作者：
EI-Shamarka, Marwa E. A.;Kozman, Magy R.;Messiha, Basim A. S.
通讯作者：
Messiha, Basim A. S.
对接和诱变研究揭示猪肝黄嘌呤氧化还原酶介导 Cyadox N-氧化物还原的机制
影响因子：
3.7
作者：
Chen C;Cheng G;Hao H;Dai M;Wang X;Huang L;Liu Z;Yuan Z
通讯作者：
Yuan Z
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
影响因子：
3.7
作者：
Breckenridge CB;Berry C;Chang ET;Sielken RL Jr;Mandel JS
通讯作者：
Mandel JS