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Action of trichostatin A on Alzheimer’s disease-like pathological changes in SH-SY5Y neuroblastoma cells

Authors :
Li-Hua Li
Wen-Na Peng
Yu Deng
Jing-Jing Li
Xiang-Rong Tian
Source :
Neural Regeneration Research, Vol 15, Iss 2, Pp 293-301 (2020)
Publication Year :
2020
Publisher :
Wolters Kluwer Medknow Publications, 2020.

Abstract

The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like epichlorohydrin-related protein-1 (Keap1) signaling pathway, amyloid β-peptide 25–35 (Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.

Details

Language :
English
ISSN :
16735374
Volume :
15
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Neural Regeneration Research
Publication Type :
Academic Journal
Accession number :
edsdoj.77a401eb3df48d4863f65d25f974094
Document Type :
article
Full Text :
https://doi.org/10.4103/1673-5374.265564