Acrylamide induces intrinsic apoptosis and inhibits protective autophagy via the ROS mediated mitochondrial dysfunction pathway in U87-MG cells

Abstract

Acrylamide (ACR) is a potential neurotoxin commonly found in the environment, as well as in food repeatedly exposed heat processing, but the mechanism underpinning ACR-induced neurotoxicity remains unclear. This study investigated the potential association and underlying signal transduction of oxidative stress, apoptosis, and autophagy associated with ACR-triggered neurotoxicity. Therefore, U87-MG cells were treated with varying ACR concentrations, while the cell activity reduction depended on the specific dosage and time parameters. Biochemical analyses showed that ACR significantly increased the reactive oxygen species (ROS), malondialdehyde (MDA), and Ca²⁺ levels while decreasing the glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), finally leading to a higher cell apoptotic rate. Moreover, ACR induced U87-MG cell apoptosis and autophagy via ROS-triggered expression in the mitochondrial apoptosis pathway, NF-κB activation, and autophagosome accumulation. In addition, the autophagosome accumulation induced by ACR could probably be ascribed to blocked autophagic flux, inhibiting the autophagosomes from combining with lysosomes, while the inhibition of autophagy caused by ACR further promoted the initiation of apoptosis. In conclusion, the results indicated that the apoptotic and autophagic pathways responded to ACR-induced neurotoxicity. However, inhibited protective autophagy further promoted apoptotic progression. New insights may be derived from these cellular responses that can help develop diverse pathway strategies for assessing the risk posed by ACR.

HIGHLIGHTS

• ACR induced mitochondrial- and caspase-dependent apoptosis in U87-MG cells.

• ACR regulated the autophagic markers and blocked autophagic flux in U87-MG cells.

• ACR inhibited protective autophagy and promoted apoptotic initiation in U87-MG cells.

Keywords:

• Acrylamide
• oxidative stress
• NF-κB activation
• intrinsic apoptosis
• protective autophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project was financially supported by the National Natural Science Foundation for Young Scientists of China [No. 31801668], the 111 Project [No. B18022], the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST [ZDXM2019], the Fundamental Research Funds for the Central Universities [No. 222201814036], and the Shanghai PuJiang Program [No. 18J1401900].