Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Ji, Jian; Zhu, Pei‐Wen; Sun, Chao; Sun, Jiadi; An, Lu; Zhang, Yinzhi; Sun, Xiulan

doi:10.2131/jts.42.43

Cited by 17 publications

(6 citation statements)

References 39 publications

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“…Two reasons can be presented for this phenomena: (1) the decrease in the dissolution of 3‐MCPD in higher doses (0.5 to 10 mM) in the cell culture medium, which led to unwanted reactions with its components, and (2) saturation of the reaction pathway of the metabolite, inhibition of metabolism pathway, and reduction in the resulting substances that have toxic properties. Despite the similarity of the results of this study and other studies conducted on the evaluation of 3‐MCPD cytotoxicity in HEK‐293 cell line and leydig cell, dose‐dependent toxicity pattern was not seen in this study (Ji et al., 2017; Peng et al., 2016; Sun et al., 2013).…”

Section: Resultscontrasting

confidence: 72%

Toxicological assessment of 3‐monochloropropane‐1,2‐diol (3‐MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway

Nazari

Naserzadeh

Dizaji

et al. 2020

Journal of Food Science

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3‐Monochloropropane‐1,2‐diol (3‐MCPD) as a main source of food contamination has always been known as a carcinogenic agent. Kidney, liver, testis, and heart seem to be the main target organs for 3‐MCPD. Because oxidative stress and mitochondrial dysfunction have been realized to be involved in 3‐MCPD‐induced cytotoxicity, the present study aimed to investigate the probable toxicity mechanisms of 3‐MCPD in isolated mitochondria, HEK‐293 cell line, and cell isolated from the rats’ liver and kidney through measuring multiparametric oxidative stress assay. Based on the data indicating no significant difference between 3‐MCPD‐treated groups and control group, metabolites of 3‐MCPD have a key role in organ toxicity caused by them. To further investigating the suggested hypothesis, the effect of 3‐MCPD toxicity on HEK‐293 cell line was examined. Although the proliferation declined after exposure to a low dose of 3‐MCPD (10 to 200 µM), controversial responses in higher concentration (2 to 10 mM) have led to studies on the effect of oxidative stress and cell death signaling on isolated kidney and liver cells. Treatment of the isolated kidney and liver cells with 3‐MCPD resulted in an increase in the level of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential (MMP), and activation of cell death signaling without creating any significant difference in the amount of reduced glutathione. In fact, 3‐MCPD can disrupt the mitochondrial electron transfer in isolated cells, which is correlated with the impairment of mitochondrial oxidative phosphorylation system, the rise of ROS level, and the failure of MMP, leading to the release of cytochrome c from mitochondria to cytosol and finally the activation of cell death signaling.

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Section: Resultscontrasting

confidence: 72%

Toxicological assessment of 3‐monochloropropane‐1,2‐diol (3‐MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway

Nazari

Naserzadeh

Dizaji

et al. 2020

Journal of Food Science

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show abstract

“…In addition, the oxidative stress event may cause the induction of mitochondrial cytochrome C which triggered by the ROS (Ji et al, 2017). Our results also supported by Mossoba et al (2020) who reported that HK-2 cells that were treated with 3-MCPD and its esters have shown slightly increased in ROS levels with the increasing concentrations of the treatment.…”

Section: Discussionsupporting

confidence: 91%

Selective Cytotoxicity Effects of R-Glycidol and S-Glycidol on Vero and HCT 116 Cells in Evaluating the Incidence of Glycidyl Esters in Edible Oils and Fats

NOR MAHIRAN1

2023

JOPR

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Despite their feasibility as food flavouring, glycidol is classified as a probable carcinogen under group 2A by WHO. The cytotoxicity effects of isomers of R-and S-glycidol on African green monkey kidney normal cell lines (Vero) and human colon cancer cell line (HCT 116) remain unclear. Cell viability of the treated Vero and HCT 116 cells was determined using the AlamarBlue® assay. Dichlorodihydrofluorescein diacetate (DCFDA) was used to evaluate reactive oxygen species (ROS) activity. Protein expressions of ERK ½, p-ERK, Bcl-2 and caspase-3 were investigated using western blotting technique. The findings indicated that R-and S-glycidol (1.16 µg/mL) exposure dramatically reduced the cell viability of the treated HCT cells but was slightly cytotoxic to Vero cells, hence triggering ROS activity. R-and S-glycidol cause down-regulation of ERK ½, p-ERK, and BCL-2 protein expression at 48 h of treatment. Furthermore, bothR-and S-glycidol possess close interaction in proximity to 3D-structure of human ERK and p-ERK protein receptors. In conclusion, Rand S-glycidol potentially triggered oxidative stress and affected ERK protein phosphorylation, leading to caspase-3 independent cell death of the treated HCT 166 cells, suggesting that lower doses (<1.16 µg/mL) of Rand S-glycidol are safe for human consumption.

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Section: Fundingmentioning

confidence: 99%

“…The cytotoxicity of 3-MCPD has been widely reported in different systems (21,(37)(38)(39). For example, 3-MCPD has been reported to trigger the death of 293 cells via the death receptor and the mitochondrial pathway (37). Furthermore, 3-MCPD has been reported to induce apoptosis in rat brain cells via activation of caspase 3 (38).…”

Section: Fundingmentioning

confidence: 99%

Activating autophagy and ferroptosis of 3‑Chloropropane‑1,2‑diol induces injury of human umbilical vein endothelial cells via AMPK/mTOR/ULK1

Xiao

Liu

2023

Mol Med Rep

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3-Chloropropane-1,2-diol (3-MCPD) is an internationally recognized food pollutant. 3-MCPD has reproductive, renal and neurotoxic properties. However, whether 3-MCPD induces human umbilical vein endothelial cell (HUVEC) injury has not been previously reported. In the present study, HUVECs were treated using 2 µg/ml 3-MCPD for 24 h at 37˚C. The effects of 3-MCPD on HUVEC proliferation and cell cycle arrest, death and senescence were then assessed using Cell Counting Kit-8 (CCK-8), flow cytometry and β-galactosidase staining, respectively. Whether 3-MCPD induced ferroptosis was evaluated using JC-1 and FerroOrange staining and transmission electron microscopy. A small interfering RNA targeting AMPK was used to assess whether 3-MCPD promoted ferroptosis via AMPK signaling. The results demonstrated that 3-MCPD inhibited HUVEC proliferation in a dose-dependent manner and induced cell cycle arrest. Furthermore, 3-MCPD promoted senescence in HUVECs with elevated DNA damage and cell death. The CCK-8 results demonstrated that ferroptosis and autophagy inhibitors significantly reversed cell death caused by 3-MCPD. Moreover, 3-MCPD increased mitochondrial membrane potential, which indicated that 3-MCPD contributed to mitochondrial dysfunction. 3-MCPD also markedly increased intracellular Fe 2+ levels and lipid peroxidation in HUVECs. The present study assessed the underlying mechanism by which 3-MCPD activated autophagy and ferroptosis in HUVECs. The data demonstrated that 3-MCPD significantly increased phosphorylation levels of AMPK and unc-51 like autophagy activating kinase (ULK1) but significantly decreased phosphorylation of mTOR in HUVECs. Furthermore, silencing of AMPK significantly reversed the increase in autophagy, lipid peroxidation and Fe 2+ induced by 3-MCPD. In conclusion, 3-MCPD demonstrated a significant damaging effect on HUVECs via induction of autophagy and ferroptosis; such effects may be mediated by AMPK/mTOR/ULK1 signaling. To the best of our knowledge, the present study was the first to demonstrate the mechanism of 3-MCPD-induced vascular endothelial cell injury and lays a molecular foundation for the prevention of 3-MCPD-related vascular diseases.

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Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

Cited by 17 publications

References 39 publications

Toxicological assessment of 3‐monochloropropane‐1,2‐diol (3‐MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway

Toxicological assessment of 3‐monochloropropane‐1,2‐diol (3‐MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway

Selective Cytotoxicity Effects of R-Glycidol and S-Glycidol on Vero and HCT 116 Cells in Evaluating the Incidence of Glycidyl Esters in Edible Oils and Fats

Activating autophagy and ferroptosis of 3‑Chloropropane‑1,2‑diol induces injury of human umbilical vein endothelial cells via AMPK/mTOR/ULK1

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