Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2022-12-15 , DOI: 10.1016/j.bbamcr.2022.119412 Mateusz Mołoń 1 , Dominika Szlachcikowska 1 , Karolina Stępień 2 , Patrycja Kielar 1 , Sabina Galiniak 2
2,2,6,6-Tetramethylpiperidine-1-oxyl, commonly known as TEMPO, is one of the compounds called nitroxides that are used in the chemical industry for synthesis of many organic compounds as well as for electrodes in all-organic radical batteries. Additionally, TEMPO is a widely used antioxidant in scientific studies. Technological progress and simultaneous care for the environment leads to resorting to new industrial methods which require the use of compounds that have not been fully tested for their impact on living organisms. Therefore, TEMPO may be an environmental pollutant and its effect on living organisms is not fully understood. The aim of our study was to determine the influence of TEMPO on the physiology, chronological lifespan and wide transcription changes of a eukaryotic model organism, namely the Saccharomyces cerevisiae yeast. For this purpose, we used the BY4741 wild-type and isogenic mutants with a disorder in the response to oxidative stress (sod1Δ, sod2Δ, yap1Δ) and repair of DNA damage (rad52Δ). We showed that supplementation with TEMPO inhibited the cell growth rate of all analyzed strains while simultaneously slowing down the aging of post-mitotic cells in the yeast population. In addition, TEMPO-treated yeast cells manifested a significantly increased level of metabolism in the wild-type and sod2Δ strains. TEMPO also displayed genoprotective effect by reducing the number of DNA double-strand breaks in cells. Here, we are the first to show the widespread effect of TEMPO on yeast. In conclusion, we have shown that, contrary to the commonly accepted notion, TEMPO has also a toxic effect, especially on active mitotic cells. We hypothesize that translation impairment or ribosome biogenesis disorder is likely to be considered secondary effects of TEMPO toxicity related to cell cycle arrest. Therefore, despite the growing interest in the use of this compound in the chemical industry, its toxic effect on the environment, especially biosphere, should be taken into account.
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl) 的两个面孔——抗氧化剂还是毒素?
2,2,6,6-Tetramethylpiperidine-1-oxyl,俗称 TEMPO,是一种称为硝基氧化物的化合物,在化学工业中用于合成许多有机化合物以及全有机基电池中的电极. 此外,TEMPO 是科学研究中广泛使用的抗氧化剂。技术进步和同时关注环境导致采用新的工业方法,这些方法需要使用尚未完全测试其对生物体影响的化合物。因此,TEMPO 可能是一种环境污染物,其对生物体的影响尚不完全清楚。我们研究的目的是确定 TEMPO 对真核模式生物的生理学、时间寿命和广泛转录变化的影响,即酿酒酵母。为此,我们使用了 BY4741 野生型和同基因突变体,这些突变体在氧化应激反应(sod1Δ、sod2Δ、yap1Δ)和 DNA 损伤修复(rad52Δ)方面存在障碍。我们发现补充 TEMPO 抑制了所有分析菌株的细胞生长速率,同时减缓了酵母群体中有丝分裂后细胞的老化。此外,TEMPO 处理的酵母细胞在野生型和sod2Δ中表现出显着增加的代谢水平菌株。TEMPO 还通过减少细胞中 DNA 双链断裂的数量显示出基因保护作用。在这里,我们是第一个展示 TEMPO 对酵母的广泛影响的人。总之,我们已经表明,与普遍接受的观念相反,TEMPO 也具有毒性作用,尤其是对活跃的有丝分裂细胞。我们假设翻译障碍或核糖体生物发生障碍可能被认为是与细胞周期停滞相关的 TEMPO 毒性的次要影响。因此,尽管人们对该化合物在化学工业中的使用越来越感兴趣,但仍应考虑其对环境,尤其是生物圈的毒性作用。