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Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.

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 (Ca²⁺), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca²⁺ 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.

SUBMITTER: Ramalingam M

PROVIDER: S-EPMC10054666 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.

Ramalingam Mahesh M Jang Sujeong S Hwang Jinsu J Kim Boeun B Cho Hyong-Ho HH Kim Eungpil E Jeong Han-Seong HS

International journal of molecular sciences 20230315 6

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 si ...[more]

PMID: 36982698

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Project description:BackgroundEndoplasmic reticulum stress (ERS) and mitochondrial dysfunction (MD) involved in bone metabolism disorders. However, the particular mechanisms of ERS and MD related genes (ERS&MDRGs) in osteoporosis (OP) have not been elucidated. In present study, biomarkers related to ERS and MD in OP were identified.MethodsDifferentially expressed genes (DEGs) were obtained based on GEO dataset. ERS&MDRGs were derived from Genecard database. Initially, ERS&MD related DEGs (ERS&MDRDEGs) were obtained by overlapping DEGs and ERS&MDRGs. The key module was screened by WGCNA. The intersection of ERS&MDRDEGs and key module was screened by machine learning to obtain key genes. Then, receiver operating characteristic curve (ROC) was drawn to calculated diagnostic accuracy of key genes. The ssGSEA and Cibersort algorithms were performed to analyze immune cell infiltration. The miRNA-mRNA-TF network were draw by cytoscape software. Moleculaer docking and DGIdb database were employed for screening potential drugs. Finally, the expression of key genes was verified by qRT-PCR.ResultsThe 122 ERS&MDRDEGs were obtained by preliminary screening. ERS&MDRDEGs were mainly enriched in lipid metabolism, calcium ion transport, and ossification. The 5 key genes were identified, including AAAS, ESR1, SLC12A2, TAF15, and VAMP2. Immune infiltration analysis showed monocyte and macrophage were different between OP and control groups. The miRNA-mRNA-TF regulatory network indicated has-miR-625-5p, has-miR-296-3p, CTCT and EP300 as potential regulatory targets. The 2 potential small molecule drugs, namely bumetanide and elacestrant were screened. The expression of AAAS, ESR1, VAMP2 were higher, and SLC12A2 and TAF15 were lower in OP than control group.ConclusionThis research identified 5 key genes AAAS, ESR1, SLC12A2, TAF15 and VAMP2. Bumetanide and elacestrant were potential drugs. These findings provided valuable insights into the pathophysiology of OP and the development of new therapeutic strategies.

Dataset Information

Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.

Publications

Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction.

Similar Datasets

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