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心理情绪应激诱导人类白细胞中卫星III(1q12)丰度和端粒重复序列发生变化,但不影响核糖体DNA。

The Psychoemotional Stress-Induced Changes in the Abundance of SatIII (1q12) and Telomere Repeats, but Not Ribosomal DNA, in Human Leukocytes.

作者信息

Umriukhin Pavel E, Ershova Elizaveta S, Filev Anton D, Agafonova Oksana N, Martynov Andrey V, Zakharova Natalia V, Veiko Roman V, Porokhovnik Lev N, Kostyuk George P, Kutsev Sergey I, Veiko Natalia N, Kostyuk Svetlana V

机构信息

Research Centre for Medical Genetics, Laboratory of Molecular Biology, 115522 Moscow, Russia.

Faculty of Normal Physiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

出版信息

Genes (Basel). 2022 Feb 14;13(2):343. doi: 10.3390/genes13020343.

Abstract

INTRODUCTION

As shown earlier, copy number variations (CNV) in the human satellite III (1q12) fragment (f-SatIII) and the telomere repeat (TR) reflects the cell's response to oxidative stress. The contents of f-SatIII and TR in schizophrenic (SZ) patients were found to be lower than in healthy controls (HC) in previous studies. The major question of this study was: 'What are the f-SatIII and TR CNV dynamic changes in human leukocytes, depending on psychoemotional stress?'

MATERIALS AND METHODS

We chose a model of psychoemotional stress experienced by second-year medical students during their exams. Blood samples were taken in stressful conditions (exams) and in a control non-stressful period. Biotinylated probes were used for f-SatIII, rDNA, and TR quantitation in leukocyte DNA by non-radioactive quantitative hybridization in SZ patients ( = 97), HC ( = 97), and medical students ( = 17, = 42). A flow cytometry analysis was used for the oxidative stress marker (NOX4, 8-oxodG, and γH2AX) detection in the lymphocytes of the three groups.

RESULTS

Oxidative stress markers increased significantly in the students' lymphocytes during psychoemotional stress. The TR and f-SatIII, but not the rDNA, contents significantly changed in the DNA isolated from human blood leukocytes. After a restoration period (post-examinational vacations), the f-SatIII content decreased, and the TR content increased. Changes in the blood cells of students during examinational stress were similar to those in SZ patients during an exacerbation of the disease.

CONCLUSIONS

Psychoemotional stress in students during exams triggers a universal mechanism of oxidative stress. The oxidative stress causes significant changes in the f-SatIII and TR contents, while the ribosomal repeat content remains stable. A hypothesis is proposed to explain the quantitative polymorphisms of f-SatIII and TR contents under transient (e.g., students' exams) or chronic (in SZ patients) stress. The changes in the f-SatIII and TR copy numbers are non-specific events, irrespective of the source of stress. Thus, our findings suggest that the psychoemotional stress, common in SZ patients and healthy students during exams, but not in a schizophrenia-specific event, was responsible for the changes in the repeat contents that we observed earlier in SZ patients.

摘要

引言

如先前所示,人类卫星III(1q12)片段(f-SatIII)和端粒重复序列(TR)中的拷贝数变异(CNV)反映了细胞对氧化应激的反应。在先前的研究中发现,精神分裂症(SZ)患者的f-SatIII和TR含量低于健康对照(HC)。本研究的主要问题是:“根据心理情绪应激,人类白细胞中f-SatIII和TR的CNV动态变化是什么?”

材料与方法

我们选择了二年级医学生考试期间经历的心理情绪应激模型。在应激条件下(考试期间)和对照非应激期采集血样。通过非放射性定量杂交,使用生物素化探针在SZ患者(n = 97)、HC(n = 97)和医学生(n = 17,n = 42)的白细胞DNA中对f-SatIII、rDNA和TR进行定量。采用流式细胞术分析检测三组淋巴细胞中的氧化应激标志物(NOX4、8-氧代脱氧鸟苷和γH2AX)。

结果

在心理情绪应激期间,学生淋巴细胞中的氧化应激标志物显著增加。从人血白细胞中分离的DNA中,TR和f-SatIII的含量显著变化,但rDNA的含量没有变化。在恢复期(考试后的假期),f-SatIII含量下降,TR含量上升。考试应激期间学生血细胞的变化与SZ患者疾病加重期间的变化相似。

结论

考试期间学生的心理情绪应激引发了氧化应激的普遍机制。氧化应激导致f-SatIII和TR含量发生显著变化,而核糖体重复序列含量保持稳定。提出了一个假设来解释在短暂(如学生考试)或慢性(SZ患者)应激下f-SatIII和TR含量的定量多态性。f-SatIII和TR拷贝数的变化是非特异性事件,与应激源无关。因此,我们的研究结果表明,SZ患者和健康学生在考试期间常见的心理情绪应激,而非精神分裂症特异性事件,是导致我们先前在SZ患者中观察到的重复序列含量变化的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/816d/8872136/9f3a03fbecf3/genes-13-00343-g001.jpg

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