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微小 RNA 作为谷胱甘肽过氧化物酶表达的潜在调节剂及其在肥胖症及相关病理中的作用。

MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies.

机构信息

Faculty of Pharmacy, Department of Biochemical Sciences, Charles University, 500 05, Hradec Králové, Czech Republic.

出版信息

Int J Mol Sci. 2018 Apr 14;19(4):1199. doi: 10.3390/ijms19041199.

Abstract

Glutathione peroxidases (GPxs) belong to the eight-member family of phylogenetically related enzymes with different cellular localization, but distinct antioxidant function. Several GPxs are important selenoproteins. Dysregulated GPx expression is connected with severe pathologies, including obesity and diabetes. We performed a comprehensive bioinformatic analysis using the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical microRNAs targeting 3'untranslated regions (3´UTR) of GPxs. We cross-referenced the literature for possible intersections between our results and available reports on identified microRNAs, with a special focus on the microRNAs related to oxidative stress, obesity, and related pathologies. We identified many microRNAs with an association with oxidative stress and obesity as putative regulators of GPxs. In particular, miR-185-5p was predicted by a larger number of programs to target six GPxs and thus could play the role as their master regulator. This microRNA was altered by selenium deficiency and can play a role as a feedback control of selenoproteins' expression. Through the bioinformatics analysis we revealed the potential connection of microRNAs, GPxs, obesity, and other redox imbalance related diseases.

摘要

谷胱甘肽过氧化物酶(GPx)属于具有不同细胞定位但具有不同抗氧化功能的进化相关酶的八个成员家族。几种 GPx 是重要的硒蛋白。GPx 表达失调与严重的疾病有关,包括肥胖和糖尿病。我们使用 miRDB、miRanda、TargetScan 和 Diana 程序进行了全面的生物信息学分析,以寻找针对 GPx 3'非翻译区(3'UTR)的假设 microRNA。我们参考文献,以确定我们的结果与已识别 microRNA 的可用报告之间可能存在的交叉点,特别关注与氧化应激、肥胖和相关病理相关的 microRNA。我们确定了许多与氧化应激和肥胖相关的 microRNA,它们可能是 GPx 的假定调节因子。特别是,miR-185-5p 被多个程序预测靶向六个 GPx,因此可以作为它们的主调控因子发挥作用。这种 microRNA 被硒缺乏所改变,并且可以作为硒蛋白表达的反馈控制发挥作用。通过生物信息学分析,我们揭示了 microRNA、GPx、肥胖和其他与氧化还原失衡相关疾病之间的潜在联系。

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