Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage

Yu, Cuiping; Pan, Yu-Lin; Wang, Xiaoli; Xin, Rui; Li, Hong-Qiu; Lei, Ya-Ting; Zhao, Fang-Fang; Zhang, Dan; Zhou, Xiaorong; Ma, Weiwei; Wang, Shengyuan; Wu, Yang‐Chang

doi:10.1016/j.ecoenv.2022.113511

Cited by 6 publications

(10 citation statements)

References 47 publications

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“…Exclusion criteria for the study encompassed long-term use of antipsychotic drugs, systemic diseases impacting the central nervous system's function, metabolic disorders, other conditions affecting blood metabolites, and diabetes resulting from prolonged medication use. Approval for the study was granted by the Ethical Committee of Harbin Medical University, and all subjects provided informed consent (Wang et al, 2020b;Yu et al, 2022).…”

Section: Study Subjectsmentioning

confidence: 99%

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Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Wang,

Zhang,

Pan

et al. 2024

Preprint

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The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. We used proteomics technology to analyze the serum of the ACR occupationally exposed population and screen out target proteins related to learning and memory. Through in vivo, in vitro experiments, and transgenic mouse models, we investigated the selected target protein to elucidate. Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomic. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. KEGG analysis indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. In summary, eEF2K as a pivotal target in the mechanisms underlying ACR-induced learning and memory impairment, providing robust evidence for potential clinical interventions targeting.

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Section: Study Subjectsmentioning

confidence: 99%

“…Individuals in the ACR exposure group utilized personal protective equipment during work, such as disposable latex gloves and dust masks. Detailed ACR concentration measurements in the ACR production workshop can be found in our prior research (Yu et al, 2022).…”

Section: Subject Characteristicsmentioning

confidence: 99%

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Wang,

Zhang,

Pan

et al. 2024

Preprint

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“…The cells were cultured in 1640 medium containing 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a 5% CO 2 incubator and passaged every two days after digestion with Trypsin-EDTA.PC12 cells were divided into the experimental group and PGK1 siRNA transfection group. The experimental group was treated with 1.25 mM and 2.5 mM acrylamide solutions, respectively, for 24 h (Yu, et al 2022). The PGK1 siRNA transfection group was treated with the same concentration of acrylamide as the experimental group, along with a pre-prepared siRNA transfection solution (final concentration of 10 μM), and other treatments were consistent with those of the experimental group.…”

Section: Cell Culture and Groupingmentioning

confidence: 99%

“…Cell viability was indirectly evaluated by CCK-8 assay (Yu, et al 2022). PC12 cells in logarithmic growth phase were seeded into 96-well plates (1×10 4 cells/well) and exposed to from experiment group and PGK1 siRNA transfection group at acrylamide concentrations of 1.25 mM and 2.5 mM for 24 h. Each group included six replicates.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…In previous studies, our research group conducted metabolomics studies on animals and humans, identifying biomarkers associated with ACR and conducting further research on them Wang, et al 2020;Yu, et al 2022). Based on the results of our earlier studies, we conducted a serum proteomics study of ACR-exposed occupational population to determine the changes caused by ACR in the human body.…”

Section: Introductionmentioning

confidence: 99%

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Inhibiting the expression of PGK1 can improve the damage of nerve cells caused by acrylamide

Wang

Pan

et al. 2023

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Recent studies have shown that phosphoglycerate kinase 1 (PGK1) may improve neurodegeneration. However, the role of PGK1 in acrylamide(ACR)-induced neuronal damage is not yet clear. In this study, SD rats were treated with 6 mg/kg and 18 mg/kg of ACR, and PC12 cells were treated with 1.25 mM and 2.5 mM of ACR, and PC12 cells were transfected with PGK1 siRNA. Behavioral responses and histopathological changes in the rats were monitored, and transmission electron microscopy was used to observe changes in neurons and internal organelles in the hippocampal tissues of the various groups. Western blot and RT-qPCR were used to detect changes in the expression of neuronal-related proteins BDNF, Syn1, Nrf2 signaling pathway-related proteins and PGK1 in the hippocampal tissues of the rats and PC12 cells. Immunohistochemistry and immunofluorescence were used to analyze PGK1 expression in the hippocampal tissues of the rats. The results showed that after ACR treatment, obvious hindlimb clasping effect was observed in rats, hippocampal tissue pathology occurred, neuronal boundaries became blurred, mitochondria swelled, and organelles became sparse. BDNF and Syn1 mRNA expression and protein levels decreased both in vivo and in vitro, while Nrf2 and PGK1 mRNA expression and protein levels increased both in vivo and in vitro. In PC12 cells, inhibition of PGK1 can alleviate cell damage, and increase the expression of BDNF and Syn1 while Nrf2 expression is suppressed. These results suggest that inhibiting the expression of PGK1 can protect nerve cell damage induced by ACR.

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A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine

Zhao

Wang

Lei

et al. 2023

Environ Sci Pollut Res

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Acrylamide is widely found in various types of fried foods and cigarettes, and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in nonsmokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can re ect acrylamide intake in the short term, which is of great signi cance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

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Stimulating the expression of sphingosine kinase 1 (SphK1) is beneficial to reduce acrylamide-induced nerve cell damage

Cited by 6 publications

References 47 publications

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

Inhibiting the expression of PGK1 can improve the damage of nerve cells caused by acrylamide

A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine

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