Abstract

BackgroundStemazole 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.MethodsSince 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.ResultsThe 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.ConclusionsIt 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.

Highlights

  • Stemazole is a novel small molecule that has been suggested to have the ability to protect multiple stem cells

  • Protein sample preparation According to previous experimental results stemazole at 40 μM was the most efficient concentration [11]. 4 days treatment was chosen according the results shown in Additional file 1: Fig. S1

  • Abundant proteins To determine the protein expression profiles affected by stemazole, we used the approach of tandem mass tags (TMT)-labelled proteomics

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Summary

Introduction

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. The small molecule compound stemazole is a potent stem cell drug that was obtained through high-throughput chemical screening of approximately 25,000 compounds. Stemazole has been found to possess great potential as a promising stem cell drug due to its prominent proliferation-promoting activity in multiple types of stem cells, such as human embryonic stem cells and human adult stem cells, including hippocampal neural/pancreatic/cardiac stem cells [11]. For human hippocampal neural stem cells, stemazole exhibits the ability to promote proliferation in a dosedependent manner and has been found to be a novel and prospective proliferative activator for stem cells [11]

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