The Role of the HIF-1α-BNIP3 Pathway in Acrylonitrile-Induced Hippocampal Neuronal Cell Toxicity †
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China
†
Presented at the 1st International Electronic Conference on Toxics, 20–22 March 2024; Available online: https://sciforum.net/event/IECTO2024.
Proceedings 2024, 102(1), 26; https://doi.org/10.3390/proceedings2024102026
Published: 28 May 2024
1. Introduction
Acrylonitrile (AN) is an important chemical raw material, and it is widely used in the production of fibers, plastics and resins. Exposure to AN occurs in occupational settings. While exposure to AN can cause neurotoxicity in bioorganisms, the exact mechanism remains unclear. Hypoxia-inducible factor (HIF) is an important transcription factor produced under hypoxia. During hypoxia, stabilized HIF-1α translocates to the nucleus and forms a dimer HIF-1 with HIF-1β, which then binds to the hypoxia-response element (HRE). Multiple downstream target genes are induced.
2. Methods
CCK assay, LDH release rate, flow cytometry, and Western blot were used to detect the cell viability, toxicity, apoptosis and expression of related proteins in hippocampal neuronal HT22 cells after exposure to AN. Then, cells were pretreated with HIF-1α activator cobalt chloride ( CoCl2) and BNIP3 overexpression, followed by the detection of relevant indicators.
3. Results
We found that the viability of HT22 cells treated with various concentrations of AN (0, 1, 2.5, 5 mM) was reduced, but LDH release rate, apoptosis, and ROS were significantly enhanced. The results of Western blotting showed that the expression of HIF-1α and its downstream proteins, including glucose transporter 1, erythropoietin, Bnip3 and NIX were decreased. In addition, due to HIF-1α CoCl2 pretreatment, cell viability and expression of HIF-1α and downstream proteins were increased. CoCl2 increased the expression of BNIP3 and BCL2 and decreased the expression of the pro-apoptosis protein BAX. However, HIF-1α inhibitor dimethoxyestradiol (2-MeOE2) showed opposite results. Furthermore, we found that cell viability was significantly increased after pretreatment with BNIP3 overexpression, increased ATP content, and co-localization of BNIP3 and LC3 seen in confocal microscopy. While the expression of TOM20 decreased, the expression of LC3B and Beclin1 increased significantly, indicating that BNIP3 mediated-mitophagy may be involved in the process.
4. Conclusions
The HIF-1α-BNIP3 pathway may participate in the neurotoxic mechanism of AN, providing an effective treatment strategy for clinical AN poisoning.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/proceedings2024102026/s1.
Funding
This work was supported by the Natural Science Foundation of China (No. 30872139, No. 81273124).
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data will be made available on request.
Conflicts of Interest
The author declares no conflict of interest.
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MDPI and ACS Style
Hu, J. The Role of the HIF-1α-BNIP3 Pathway in Acrylonitrile-Induced Hippocampal Neuronal Cell Toxicity. Proceedings 2024, 102, 26. https://doi.org/10.3390/proceedings2024102026
AMA Style
Hu J. The Role of the HIF-1α-BNIP3 Pathway in Acrylonitrile-Induced Hippocampal Neuronal Cell Toxicity. Proceedings. 2024; 102(1):26. https://doi.org/10.3390/proceedings2024102026
Chicago/Turabian StyleHu, Jing. 2024. "The Role of the HIF-1α-BNIP3 Pathway in Acrylonitrile-Induced Hippocampal Neuronal Cell Toxicity" Proceedings 102, no. 1: 26. https://doi.org/10.3390/proceedings2024102026
