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Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction
Mesenchymal stem cells (MSCs) have therapeutic effects on neurodegenerative diseases (NDDs) known by their secreted molecules, referred to as the “secretome”. The mitochondrial complex I inhibitor, rotenone (ROT), reproduces α-synuclein (α-syn) aggregation seen in Parkinson’s disease (PD). In this p...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054666/ https://www.ncbi.nlm.nih.gov/pubmed/36982698 http://dx.doi.org/10.3390/ijms24065622 |
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author | Ramalingam, Mahesh Jang, Sujeong Hwang, Jinsu Kim, Boeun Cho, Hyong-Ho Kim, Eungpil Jeong, Han-Seong |
author_facet | Ramalingam, Mahesh Jang, Sujeong Hwang, Jinsu Kim, Boeun Cho, Hyong-Ho Kim, Eungpil Jeong, Han-Seong |
author_sort | Ramalingam, Mahesh |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) have therapeutic effects on neurodegenerative diseases (NDDs) known by their secreted molecules, referred to as the “secretome”. The mitochondrial complex I inhibitor, rotenone (ROT), reproduces α-synuclein (α-syn) aggregation seen in Parkinson’s disease (PD). In this present study, we examined the neuroprotective effects of the secretome from neural-induced human adipose tissue-derived stem cells (NI-ADSC-SM) during ROT toxicity in SH-SY5Y cells. Exposure to ROT significantly impaired the mitophagy by increased LRRK2, mitochondrial fission, and endoplasmic reticulum (ER) stress (ERS). ROT also increased the levels of calcium (Ca(2+)), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca(2+) levels along with LRRK2, insoluble ubiquitin, mitochondrial fission by halting p-DRP1 Ser616, ERS by reducing p-PERK Thr981, p-/t-IRE1α, p-SAPK, ATF4, and CHOP. In addition, NI-ADSC-SM restored the mitophagy, mitochondrial fusion, and tethering to the ER. These data suggest that NI-ADSC-SM decreases ROT-induced dysfunction in mitochondria and the ER, which subsequently stabilized tethering in mitochondria-associated membranes in SH-SY5Y cells. |
format | Online Article Text |
id | pubmed-10054666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100546662023-03-30 Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction Ramalingam, Mahesh Jang, Sujeong Hwang, Jinsu Kim, Boeun Cho, Hyong-Ho Kim, Eungpil Jeong, Han-Seong Int J Mol Sci Article Mesenchymal stem cells (MSCs) have therapeutic effects on neurodegenerative diseases (NDDs) known by their secreted molecules, referred to as the “secretome”. The mitochondrial complex I inhibitor, rotenone (ROT), reproduces α-synuclein (α-syn) aggregation seen in Parkinson’s disease (PD). In this present study, we examined the neuroprotective effects of the secretome from neural-induced human adipose tissue-derived stem cells (NI-ADSC-SM) during ROT toxicity in SH-SY5Y cells. Exposure to ROT significantly impaired the mitophagy by increased LRRK2, mitochondrial fission, and endoplasmic reticulum (ER) stress (ERS). ROT also increased the levels of calcium (Ca(2+)), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca(2+) levels along with LRRK2, insoluble ubiquitin, mitochondrial fission by halting p-DRP1 Ser616, ERS by reducing p-PERK Thr981, p-/t-IRE1α, p-SAPK, ATF4, and CHOP. In addition, NI-ADSC-SM restored the mitophagy, mitochondrial fusion, and tethering to the ER. These data suggest that NI-ADSC-SM decreases ROT-induced dysfunction in mitochondria and the ER, which subsequently stabilized tethering in mitochondria-associated membranes in SH-SY5Y cells. MDPI 2023-03-15 /pmc/articles/PMC10054666/ /pubmed/36982698 http://dx.doi.org/10.3390/ijms24065622 Text en © 2023 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 Ramalingam, Mahesh Jang, Sujeong Hwang, Jinsu Kim, Boeun Cho, Hyong-Ho Kim, Eungpil Jeong, Han-Seong Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title | Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title_full | Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title_fullStr | Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title_full_unstemmed | Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title_short | Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction |
title_sort | neuroprotective effects of the neural-induced adipose-derived stem cell secretome against rotenone-induced mitochondrial and endoplasmic reticulum dysfunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054666/ https://www.ncbi.nlm.nih.gov/pubmed/36982698 http://dx.doi.org/10.3390/ijms24065622 |
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