Li Huajun, Zhang Yubo, Zhang Jing, Zhao Chaoran, Zhu Yizi, Han Mei
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
Proteome Sci. 2020 Dec 9;18(1):12. doi: 10.1186/s12953-020-00168-2.
Stemazole is a novel small molecule that has been suggested to have the ability to protect multiple stem cells. The proliferation-promoting activity and promising neuroprotective effects of stemazole make it a prospective drug for neurodegenerative disease treatment.
Since previous studies have shown that it protective effect in extreme conditions, to understand more aspects of stemazole, in this study, a systematic tandem mass tags (TMT)-labelled proteomics approach was used to address the whole proteome expression profile with or without stemazole in normal conditions instead of extreme conditions. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) network analyses, were employed.
The effect of stemazole on the expression profiles of neural stem cells was obtained. A total of 408 proteins with changes at the abundance level of two groups were identified: 178 proteins increase in abundance and 240 proteins decrease in abundance, respectively. Low abundance of some mitochondrial respiratory chain enzyme, overproduction of reactive oxygen species (ROS) and reduction of mitochondrial membrane potential may indicate stemazole has cytotoxicity.
It is the first proteomics research about stemazole, and the possible cytotoxicity of stemazole has been reported for the first time. The information about proteins that were affected by stemazole and more characteristics of stemazole will help obtain a complete picture of this small molecule drug. These findings provide a scientific basis for further stemazole treatment research.
司他唑是一种新型小分子,已被证明具有保护多种干细胞的能力。司他唑的促增殖活性和有前景的神经保护作用使其成为治疗神经退行性疾病的一种有潜力的药物。
由于先前的研究表明其在极端条件下具有保护作用,为了更全面地了解司他唑,在本研究中,采用了系统的串联质谱标签(TMT)标记蛋白质组学方法,以研究在正常而非极端条件下有无司他唑时的全蛋白质组表达谱。进行了生物信息学分析,包括基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路富集和蛋白质-蛋白质相互作用(PPI)网络分析。
获得了司他唑对神经干细胞表达谱的影响。共鉴定出408种在两组丰度水平上有变化的蛋白质:丰度增加的蛋白质有178种,丰度降低的蛋白质有240种。一些线粒体呼吸链酶丰度降低、活性氧(ROS)过量产生以及线粒体膜电位降低可能表明司他唑具有细胞毒性。
这是关于司他唑的首次蛋白质组学研究,首次报道了司他唑可能具有的细胞毒性。受司他唑影响的蛋白质信息以及司他唑的更多特性将有助于全面了解这种小分子药物。这些发现为进一步研究司他唑治疗提供了科学依据。