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葡萄糖-6-磷酸脱氢酶缺陷小鼠中肝脏转录谱对蚕豆诱导的氧化应激的反应

Hepatic transcriptional profiling response to fava bean-induced oxidative stress in glucose-6-phosphate dehydrogenase-deficient mice.

作者信息

Du Guankui, Xiao Man, Wei Xiuyu, Zhou Chen, Li Shuoshuo, Cai Wangwei

机构信息

Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou 571199, China.

Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou 571199, China.

出版信息

Gene. 2018 Apr 30;652:66-77. doi: 10.1016/j.gene.2018.02.014. Epub 2018 Feb 8.

DOI:10.1016/j.gene.2018.02.014
PMID:29428800
Abstract

Favism is an acute hemolytic syndrome caused by the ingestion of fava bean (FB) in glucose 6-phosphate dehydrogenase (G6PD) deficient individuals. However, little is known about the global transcripts alteration in liver tissue after FB ingestion in G6PD-normal and -deficient states. In this study, deep sequencing was used to analyze liver genes expression alterations underlying the effects of FB in C3H (Wild Type, WT) and G6PD-deficient (G6PDx) mice and to evaluate and visualize the collective annotation of a list of genes to Gene Ontology (GO) terms associated with favism. Our results showed that FB resulted in a decrease of glutathione (GSH)-to-oxidized glutathione (GSSG) ratio and an increase of malondialdehyde (MDA) both in the G6PDx and WT-control check (CK) mice plasma. Significantly, liver transcript differences were observed between the control and FB-treated groups of both WT and G6PDx mice. A total of 320 differentially expressed transcripts were identified by comparison of G6PDx-CK with WT-CK and were associated with immune response and oxidation-reduction function. A total of 149 differentially expressed genes were identified by comparison of WT-FB with WT-CK. These genes were associated with immune response, steroid metabolic process, creatine kinase activity, and fatty acid metabolic process. A total of 438 differential genes were identified by comparing G6PDx-FB with G6PD-CK, associated with the negative regulation of fatty acid metabolic process, endoplasmic reticulum, iron binding, and glutathione transferase activity. These findings indicate that G6PD mutations may affect the functional categories such as immune response and oxidation-reduction.

摘要

蚕豆病是一种急性溶血性综合征,由葡萄糖6 - 磷酸脱氢酶(G6PD)缺乏的个体摄入蚕豆(FB)引起。然而,对于G6PD正常和缺乏状态下摄入FB后肝脏组织中的全局转录本变化知之甚少。在本研究中,深度测序用于分析FB对C3H(野生型,WT)和G6PD缺乏(G6PDx)小鼠肝脏基因表达的影响,并评估和可视化与蚕豆病相关的基因列表对基因本体(GO)术语的集体注释。我们的结果表明,FB导致G6PDx和WT对照(CK)小鼠血浆中谷胱甘肽(GSH)与氧化型谷胱甘肽(GSSG)的比率降低,丙二醛(MDA)增加。值得注意的是,WT和G6PDx小鼠的对照组与FB处理组之间均观察到肝脏转录本差异。通过比较G6PDx - CK与WT - CK,共鉴定出320个差异表达的转录本,它们与免疫反应和氧化还原功能相关。通过比较WT - FB与WT - CK,共鉴定出149个差异表达基因。这些基因与免疫反应、类固醇代谢过程、肌酸激酶活性和脂肪酸代谢过程相关。通过比较G6PDx - FB与G6PD - CK,共鉴定出438个差异基因,它们与脂肪酸代谢过程的负调控、内质网、铁结合和谷胱甘肽转移酶活性相关。这些发现表明,G6PD突变可能影响免疫反应和氧化还原等功能类别。

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