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A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells

Neurodegenerative disorders have become a serious healthcare problem worldwide and there is no efficacious cure. However, regulating the fate of stem cells is an effective way to treat these neurological diseases. In previous work, stemazole was reported to maintain the survival of human neural stem...

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Autores principales: Chen, Mingzhu, Zhu, Yizi, Li, Huajun, Zhang, Yubo, Han, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221083/
https://www.ncbi.nlm.nih.gov/pubmed/35741576
http://dx.doi.org/10.3390/brainsci12060690
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author Chen, Mingzhu
Zhu, Yizi
Li, Huajun
Zhang, Yubo
Han, Mei
author_facet Chen, Mingzhu
Zhu, Yizi
Li, Huajun
Zhang, Yubo
Han, Mei
author_sort Chen, Mingzhu
collection PubMed
description Neurodegenerative disorders have become a serious healthcare problem worldwide and there is no efficacious cure. However, regulating the fate of stem cells is an effective way to treat these neurological diseases. In previous work, stemazole was reported to maintain the survival of human neural stem cells in the absence of growth factors and to have therapeutic effects on neurodegenerative diseases. However, although it is a promising small molecule, the molecular mechanisms against apoptosis are ambiguous. In this study, tandem mass tag (TMT)-based proteomics were performed to obtain whole protein expression profiles of human neural stem cells in different groups under extreme conditions. Bioinformatics analysis based on protein–protein interaction (PPI) network construction, gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were adopted to explore crucial proteins and possible pharmacological mechanisms. A total of 77 differentially expressed proteins were identified, comprising 38 upregulated proteins and 39 downregulated proteins. Combined with a diseases database of Alzheimer’s disease (AD), caspase-2 (CASP2), PKA C-alpha (PRKACA), fibronectin (FN1), large neutral amino acid transporter small subunit 1 (SLC7A5), which are involved in cell proliferation and apoptosis, this was further validated by enzyme activity assay and molecular docking, and regarded as putative targets regulated by stemazole. The present results give an insight into this small molecule and a better understanding for further elucidating the underlying mechanisms in the treatment of stem cells and neurodegenerative diseases.
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spelling pubmed-92210832022-06-24 A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells Chen, Mingzhu Zhu, Yizi Li, Huajun Zhang, Yubo Han, Mei Brain Sci Article Neurodegenerative disorders have become a serious healthcare problem worldwide and there is no efficacious cure. However, regulating the fate of stem cells is an effective way to treat these neurological diseases. In previous work, stemazole was reported to maintain the survival of human neural stem cells in the absence of growth factors and to have therapeutic effects on neurodegenerative diseases. However, although it is a promising small molecule, the molecular mechanisms against apoptosis are ambiguous. In this study, tandem mass tag (TMT)-based proteomics were performed to obtain whole protein expression profiles of human neural stem cells in different groups under extreme conditions. Bioinformatics analysis based on protein–protein interaction (PPI) network construction, gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were adopted to explore crucial proteins and possible pharmacological mechanisms. A total of 77 differentially expressed proteins were identified, comprising 38 upregulated proteins and 39 downregulated proteins. Combined with a diseases database of Alzheimer’s disease (AD), caspase-2 (CASP2), PKA C-alpha (PRKACA), fibronectin (FN1), large neutral amino acid transporter small subunit 1 (SLC7A5), which are involved in cell proliferation and apoptosis, this was further validated by enzyme activity assay and molecular docking, and regarded as putative targets regulated by stemazole. The present results give an insight into this small molecule and a better understanding for further elucidating the underlying mechanisms in the treatment of stem cells and neurodegenerative diseases. MDPI 2022-05-25 /pmc/articles/PMC9221083/ /pubmed/35741576 http://dx.doi.org/10.3390/brainsci12060690 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Mingzhu
Zhu, Yizi
Li, Huajun
Zhang, Yubo
Han, Mei
A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title_full A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title_fullStr A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title_full_unstemmed A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title_short A Quantitative Proteomic Approach Explores the Possible Mechanisms by Which the Small Molecule Stemazole Promotes the Survival of Human Neural Stem Cells
title_sort quantitative proteomic approach explores the possible mechanisms by which the small molecule stemazole promotes the survival of human neural stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221083/
https://www.ncbi.nlm.nih.gov/pubmed/35741576
http://dx.doi.org/10.3390/brainsci12060690
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