Notoginsenoside R1 Protects Against the Acrylamide-Induced Neurotoxicity via Upregulating Trx-1-Mediated ITGAV Expression: Involvement of Autophagy.

Wenjun Wang,Yingying Hu,Xiang Li,Elizabeth Rosalind Thomas,Lu Huang,Fancai Zeng

doi:10.3389/fphar.2020.559046

Wenjun Wang, Yingying Hu + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2020.559046

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Abstract

Acrylamide (ACR) is a common chemical used in various industries and it said to have chronic neurotoxic effects. It is produced during tobacco smoking and is also generated in high-starch foods during heat processing. Notoginsenoside R1 (NR1) is a traditional Chinese medicine, which is used to improve the blood circulation and clotting. The objective of this study was to investigate the mechanism of ACR-triggered neurotoxicity and to identify the protective role of NR1 by upregulating thioredoxin-1 (Trx-1). Our results have shown that NR1 could block the spatial and cognitive impairment caused by ACR administration. Bioinformatics analysis revealed that Trx-1 regulated autophagy via Integrin alpha V (ITGAV). NR1 could resist the ACR-induced neurotoxicity by upregulating thioredoxin-1 in PC12 cells and mice. The autophagy-related proteins like autophagy-related gene (ATG) 4B, Cathepsin D, LC3 II, lysosomal-associated membrane protein 2a (LAMP2a), and ITGAV were restored to normal levels by NR1 treatment in both PC12 cells and mice. Besides, we also found that overexpression of Trx-1 resisted ACR-induced autophagy in PC12 cells and downregulation of Trx-1 triggered autophagy induced by ACR in PC12 cells. Therefore, it could be concluded that Trx-1 was involved in the autophagy pathway. Besides, we also found that ITGAV was an intermediate node linking Trx-1 and the autophagy pathway.

Highlights

Acrylamide (ACR), a well-known water-soluble chemical, is extensively used in various industries
By using bioinformatics analysis, our results have proven the neuroprotective properties of Notoginsenoside R1 (NR1) on ACR-induced autophagy in PC12 cells
We found that the increase in the levels of ATG4B, LC3II, Cathepsin D, and lysosomal-associated membrane protein 2a (LAMP2a) expression induced by ACR were repressed by NR1

Summary

Introduction

Acrylamide (ACR), a well-known water-soluble chemical, is extensively used in various industries. Because of its wide application, human beings are exposed to high levels of ACR (Adewale et al, 2015). Neurotoxicity is a typical phenomenon of ACR toxicity in animal and cell models. NR1 Suppressed ACR-Induced Neurotoxicity toxicity could induce cogitative deficits by influencing the autophagic function of the neurons in the hippocampus (Hip) (Tan et al, 2019). It was found that ACR-induced cellular toxicity in neurons could lead to apoptosis (He et al, 2017), mitochondrial dysfunction (Zamani et al, 2017), and downregulate antioxidant signaling pathway (Pan et al, 2017). The relationship between ACR and autophagy in PC12 cells still remains unmapped

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