Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ25-35

Xinwei Wu,Guoyong Jia,Congcong Sun,Zengyan Diao,Ying Liu,Hongna Yang

doi:10.32604/biocell.2021.015701

Abstract

A progressive neurodegenerative disease, Alzheimer’s disease (AD). Studies suggest that highly expressed protein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects of neural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ25-35-induced damage in SH-SY5Y cells. Our data suggested that Aβ25-35 markedly inhibited cell viability. NSC-CDM or Neural stem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ25-35, with a greater effect observed with NSC-CDM. Aβ25-35 + NSC-CDM group exhibited an increase in PCMT1 expression. sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression. Overexpression of PCMT1 reversed the Aβ25-35-induced decrease in cell proliferation and apoptosis. In summary, our findings suggest that NSC-CDM corrects the Aβ25-35- induced damage to cells by improving PCMT1 expressions, which in turn reduces phosphorylation of MST1.

Highlights

Alzheimer’s disease (AD) is a multifactorial disease with multiple risk factors
The pathological mechanisms of AD include the deposition of amyloid β (Aβ), astroglia degeneration, hyperphosphorylation and accumulation of the tau protein, neuronal dystrophy, oxidative stress, mitochondrial dysfunction, biological metal homeostasis, and decreased levels of acetylcholine (ACh) (Butterfield et al, 2001; Reddy, 2011)
The SH-SY5Y cells culture and the groups were divided as follows: control group; Aβ25-35 group; Aβ25-35 + Neural stem cell-complete medium (NSC-CPM) group; Aβ25-35 + neural stem cell-conditioned medium (NSC-CDM) group according to our previous study (Jia et al, 2020)

Summary

Introduction

The pathological mechanisms of AD include the deposition of amyloid β (Aβ), astroglia degeneration, hyperphosphorylation and accumulation of the tau protein, neuronal dystrophy, oxidative stress, mitochondrial dysfunction, biological metal homeostasis, and decreased levels of acetylcholine (ACh) (Butterfield et al, 2001; Reddy, 2011). Many studies have shown that PCMT1 acts a critical effect in the regulation of longevity, different types of oxidative stress, heat shock response, and apoptosis (Aleksandra et al, 2014; Jost et al, 2002). The up-regulation of PCMT1 is related to the decrease of neurodegenerative factor levels and the anti-apoptotic effect of neurons, thereby inhibiting cerebral edema (Liang et al, 2017; Shi et al, 2017a)

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