Reduced sirtuin 1/adenosine monophosphate-activated protein kinase in amyotrophic lateral sclerosis patient-derived mesenchymal stem cells can be restored by resveratrol
- Authors
- Yun, Young Chan; Jeong, Sin-Gu; Kim, Seung Hyun; Cho, Goang-Won
- Issue Date
- Jan-2019
- Publisher
- WILEY
- Keywords
- AMPK; amyotrophic lateral sclerosis; mesenchymal stem cells; neuronal differentiation; resveratrol; SIRT1
- Citation
- JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v.13, no.1, pp.110 - 115
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
- Volume
- 13
- Number
- 1
- Start Page
- 110
- End Page
- 115
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/148496
- DOI
- 10.1002/term.2776
- ISSN
- 1932-6254
- Abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neuron system. Our previous study has shown that bone marrow-mesenchymal stem cells (BM-MSCs) from ALS patients have functional limitations in releasing neurotrophic factors and exhibit the senescence phenotype. In this study, we examined sirtuin 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) activities and identified significant decreases in the ALS-MSCs compared with normal healthy control originated BM-MSCs. This decline was restored by pretreatment with resveratrol (RSV), measured using quantitative polymerase chain reaction, NAD/NADH assay, and immunoblot analysis. Neuroprogenitor markers were increased in RSV-treated ALS-MSCs (RSV/ALS-MSCs). The differentiated ALS-MSCs (ALS-dMSCs) exhibited a cell body and dendritic shape similar to neurons. RSV/ALS-MSCs showed significantly increased differentiation rate as compared with the untreated ALS-dMSCs. The neurite numbers and lengths were also significantly increased. This was confirmed with immunoblot analysis using neuron specific markers such as nestin, NF-M, Tuj-1, and Map-2 in RSV/ALS-dMSCs. Thus, this study shows that ALS-MSCs showed down-regulation of AMPK/SIRT1 signalling, which was recovered by treatment with RSV. This data suggest that RSV can be one of the candidate agents for improving therapeutic efficacy of ALS patients' originated MSCs.
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