Activating autophagy and ferroptosis of 3‑Chloropropane‑1,2‑diol induces injury of human umbilical vein endothelial cells via AMPK/mTOR/ULK1 Retraction in /10.3892/mmr.2024.13377

Yi,Xin; Long,Xiao; Liu,Canzhang

doi:10.3892/mmr.2023.12963

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

Retraction in: /10.3892/mmr.2024.13377

Authors:
- Xin Yi
- Xiao Long
- Canzhang Liu
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Affiliations: Department of Cardiovasology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: February 15, 2023 https://doi.org/10.3892/mmr.2023.12963
Article Number: 76
Copyright: © Yi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 Fe2+ 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 Fe²⁺ 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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