Association between oxidative stress and microRNA expression pattern of ALS patients in the high-incidence area of the Kii Peninsula
Association between oxidative stress and microRNA expression pattern of ALS patients in the high-incidence area of the Kii Peninsula
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DOI：
10.1016/j.brainres.2020.147035
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发表时间：
2020-11-01
期刊：
影响因子：
2.9
通讯作者：
Kihira, Tameko
中科院分区：
文献类型：
--
作者：
Arakawa, Yuya;Itoh, Shunji;Kihira, Tameko
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种上、下运动神经元系统的进行性退行性疾病。20世纪60年代，日本纪伊半岛南部（K-ALS）的ALS发病率很高，但已逐渐降至世界平均水平。虽然该地区ALS高发病率的原因尚不清楚，但我们以前的研究表明，环境因素，包括必需矿物质缺乏和金属诱导的氧化应激增加，在其发展中发挥作用。近年来，有研究发现microRNA（microRNA，miRNA）参与了神经系统的退行性变，如ALS。本研究的目的是探索K-ALS中的特异性miRNAs，并评估氧化应激之间的关系。我们综合分析了K-ALS患者、散发性ALS（S-ALS）、本地区居民（K-residents）和来自其他地区的对照者的血清miRNAs和尿8-羟基-2 '-脱氧鸟苷（8-OHdG）、血清Cu/Zn超氧化物歧化酶（SOD）和血清N ε-己酰赖氨酸（HEL）作为氧化应激标志物。K-ALS患者中miR-92 a-3 p和miR-486- 5 p的表达水平显著高于对照组。K-ALS患者的HEL水平显著高于S-ALS患者和对照组。miR-92 a-3 p和miR-486- 5 p的表达水平与HEL水平无相关性。一组高水平的miR-92 a-3 p、miR-486- 5 p和血清HEL可能是Kii半岛K-ALS的有用生物标志物。研究结果应进一步研究了大量的科目。
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder of the upper and lower motor neuron systems. The high incidence of ALS in the southern part of the Kii Peninsula of Japan (K-ALS) was reported in the 1960s, but it has gradually decreased to the worldwide average. Although causes of the high incidence of ALS in this area are unknown, our previous studies suggested that environmental factors, including essential mineral deficiency and increased metal-induced oxidative stress, play a role in its development. Recently, it has been reported that microRNAs (miRNA) contribute to the degeneration of nervous system such as ALS. The aim of this study is to explore specific miRNAs in K-ALS and evaluate relationships between oxidative stress. We comprehensively analyzed serum miRNAs and examined urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), serum Cu/Zn superoxide dismutase (SOD) and serum N epsilon-hexanoyl lysin (HEL) as oxidative stress markers in the patients with K-ALS, sporadic ALS (S-ALS), residents in this area (K-residents) and controls from another area. The expression levels of miR-92a-3p and miR-486-5p in the patients with K-ALS were significantly higher than those in controls. The HEL levels were significantly higher in the patients with K-ALS than in those with S-ALS and controls. The expression levels of miR-92a-3p and miR-486-5p were not correlated with the levels of HEL. A set of high levels of miR-92a-3p, miR-486-5p and serum HEL may be a useful biomarker for K-ALS in the Kii Peninsula. The findings should be further studied by a large number of subjects.