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Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2023 Mar 15; Vol. 24 (6). Date of Electronic Publication: 2023 Mar 15. - Publication Year :
- 2023
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Abstract
- 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 <superscript>2+</superscript> ), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca <superscript>2+</superscript> 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.
- Subjects :
- Humans
Rotenone toxicity
Endoribonucleases metabolism
Protein Serine-Threonine Kinases metabolism
Endoplasmic Reticulum metabolism
Mitochondria metabolism
Endoplasmic Reticulum Stress
Neuroprotective Agents pharmacology
Neuroprotective Agents metabolism
Neuroblastoma metabolism
Neural Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36982698
- Full Text :
- https://doi.org/10.3390/ijms24065622