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在琥珀酸脱氢酶亚基B的酵母模型中解析一种新型种系错义突变(R38C)的功能后果:对神经退行性疾病的见解

Unraveling the functional consequences of a novel germline missense mutation (R38C) in the yeast model of succinate dehydrogenase subunit B: insights into neurodegenerative disorders.

作者信息

Zheng Jiatong, Liu Siru, Wang Dongdong, Li Linlin, Sarsaiya Surendra, Zhou Hua, Cai Heng

机构信息

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China.

出版信息

Front Mol Neurosci. 2023 Sep 28;16:1246842. doi: 10.3389/fnmol.2023.1246842. eCollection 2023.

DOI:10.3389/fnmol.2023.1246842
PMID:37840772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10568460/
Abstract

This study explores the implications of a novel germline missense mutation (R38C) in the succinate dehydrogenase (SDH) subunit B, which has been linked to neurodegenerative diseases. The mutation was identified from the SDH mutation database and corresponds to the allele, mirroring the human mutation. By subjecting the mutant yeast model to hydrogen peroxide (HO) stress, simulating oxidative stress, we observed heightened sensitivity to oxidative conditions. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed significant regulation ( < 0.05) of genes associated with antioxidant systems and energy metabolism. Through gas chromatography-mass spectrometry (GC-MS) analysis, we examined yeast cell metabolites under oxidative stress, uncovering insights into the potential protective role of o-vanillin. This study elucidates the biological mechanisms underlying cellular oxidative stress responses, offering valuable insights into its repercussions. These findings shed light on innovative avenues for addressing neurodegenerative diseases, potentially revolutionizing therapeutic strategies.

摘要

本研究探讨了琥珀酸脱氢酶(SDH)亚基B中一种新的种系错义突变(R38C)的影响,该突变与神经退行性疾病有关。该突变是从SDH突变数据库中鉴定出来的,与等位基因相对应,反映了人类突变。通过使突变酵母模型遭受过氧化氢(HO)应激,模拟氧化应激,我们观察到对氧化条件的敏感性增加。定量实时逆转录聚合酶链反应(qRT-PCR)分析显示,与抗氧化系统和能量代谢相关的基因有显著调控(<0.05)。通过气相色谱-质谱(GC-MS)分析,我们检测了氧化应激下酵母细胞的代谢产物,揭示了邻香草醛潜在的保护作用。本研究阐明了细胞氧化应激反应的生物学机制,为其影响提供了有价值的见解。这些发现为解决神经退行性疾病的创新途径提供了线索,可能会彻底改变治疗策略。

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