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Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway
Oxidative stress damage is a common problem in bone marrow mesenchymal stem cell (BMSC) transplantation. Under stress conditions, the mitochondrial function of BMSCs is disrupted, which accelerates senescence and apoptosis of BMSCs, ultimately leading to poor efficacy. Therefore, improving mitochond...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762348/ https://www.ncbi.nlm.nih.gov/pubmed/34981121 http://dx.doi.org/10.1042/BSR20211005 |
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author | Wang, Tao Zhang, Fei Peng, Wuxun Wang, Lei Zhang, Jian Dong, Wentao Tian, Xiaobin Ye, Chuan Li, Yanlin Gong, Yuekun |
author_facet | Wang, Tao Zhang, Fei Peng, Wuxun Wang, Lei Zhang, Jian Dong, Wentao Tian, Xiaobin Ye, Chuan Li, Yanlin Gong, Yuekun |
author_sort | Wang, Tao |
collection | PubMed |
description | Oxidative stress damage is a common problem in bone marrow mesenchymal stem cell (BMSC) transplantation. Under stress conditions, the mitochondrial function of BMSCs is disrupted, which accelerates senescence and apoptosis of BMSCs, ultimately leading to poor efficacy. Therefore, improving mitochondrial function and enhancing the antioxidative stress capacity of BMSCs may be an effective way of improving the survival rate and curative effect of BMSCs. In the present study, we have confirmed that overexpression of nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) improves mitochondrial function and resistance to stress-induced apoptosis in BMSCs. We further revealed the mechanism of NMNAT3-mediated resistance to stress-induced apoptosis in BMSCs. We increased the level of nicotinamide adenine dinucleotide (NAD(+)) by overexpressing NMNAT3 in BMSCs and found that it could significantly increase the activity of silent mating type information regulation 2 homolog 3 (Sirt3) and significantly decrease the acetylation levels of Sirt3-dependent deacetylation-related proteins isocitrate dehydrogenase 2 (Idh2) and Forkhead-box protein O3a (FOXO3a). These findings show that NMNAT3 may increase the activity of Sirt3 by increasing NAD(+) levels. Our results confirm that the NMNAT3-NAD(+)-Sirt3 axis is a potential mechanism for improving mitochondrial function and enhancing antioxidative stress capacity of BMSCs. In the present study, we take advantage of the role of NMNAT3 in inhibiting stress-induced apoptosis of BMSCs and provide new methods and ideas for breaking through the bottleneck of transplantation efficacy of BMSCs in the clinic. |
format | Online Article Text |
id | pubmed-8762348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87623482022-01-25 Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway Wang, Tao Zhang, Fei Peng, Wuxun Wang, Lei Zhang, Jian Dong, Wentao Tian, Xiaobin Ye, Chuan Li, Yanlin Gong, Yuekun Biosci Rep Cell Death & Injury Oxidative stress damage is a common problem in bone marrow mesenchymal stem cell (BMSC) transplantation. Under stress conditions, the mitochondrial function of BMSCs is disrupted, which accelerates senescence and apoptosis of BMSCs, ultimately leading to poor efficacy. Therefore, improving mitochondrial function and enhancing the antioxidative stress capacity of BMSCs may be an effective way of improving the survival rate and curative effect of BMSCs. In the present study, we have confirmed that overexpression of nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) improves mitochondrial function and resistance to stress-induced apoptosis in BMSCs. We further revealed the mechanism of NMNAT3-mediated resistance to stress-induced apoptosis in BMSCs. We increased the level of nicotinamide adenine dinucleotide (NAD(+)) by overexpressing NMNAT3 in BMSCs and found that it could significantly increase the activity of silent mating type information regulation 2 homolog 3 (Sirt3) and significantly decrease the acetylation levels of Sirt3-dependent deacetylation-related proteins isocitrate dehydrogenase 2 (Idh2) and Forkhead-box protein O3a (FOXO3a). These findings show that NMNAT3 may increase the activity of Sirt3 by increasing NAD(+) levels. Our results confirm that the NMNAT3-NAD(+)-Sirt3 axis is a potential mechanism for improving mitochondrial function and enhancing antioxidative stress capacity of BMSCs. In the present study, we take advantage of the role of NMNAT3 in inhibiting stress-induced apoptosis of BMSCs and provide new methods and ideas for breaking through the bottleneck of transplantation efficacy of BMSCs in the clinic. Portland Press Ltd. 2022-01-14 /pmc/articles/PMC8762348/ /pubmed/34981121 http://dx.doi.org/10.1042/BSR20211005 Text en © 2022 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Cell Death & Injury Wang, Tao Zhang, Fei Peng, Wuxun Wang, Lei Zhang, Jian Dong, Wentao Tian, Xiaobin Ye, Chuan Li, Yanlin Gong, Yuekun Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title | Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title_full | Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title_fullStr | Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title_full_unstemmed | Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title_short | Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD(+)-Sirt3 pathway |
title_sort | overexpression of nmnat3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the nad(+)-sirt3 pathway |
topic | Cell Death & Injury |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762348/ https://www.ncbi.nlm.nih.gov/pubmed/34981121 http://dx.doi.org/10.1042/BSR20211005 |
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