Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of toxicants on endoplasmic reticulum stress and hepatic cell fate determination

  • Jihoon Tak (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul) ;
  • Sang Geon Kim (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul)
  • Received : 2023.05.09
  • Accepted : 2023.06.29
  • Published : 2023.10.15
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Abstract

Toxicant-induced injury is a significant global health issue. However, the mechanisms through which toxicants such as carbon tetrachloride, acetaminophen, dimethylformamide, cocaine, and morphine induce the death of multiple cell types and contribute to liver toxicity are highly complex. This phenomenon involves intricate signaling pathways in association with oxidative stress, inflammation, and activation of death receptors, which are closely linked to endoplasmic reticulum (ER) stress. ER stress initially triggers the unfolded protein response, which either promotes cell survival or causes cell death at later times, depending on the severity and duration of the stress. Thus, comprehending the molecular basis governing cell fate determination in the context of ER stress may provide key insights into the prevention and treatment of toxicant-induced injury. This review summarizes our current understanding of agents that trigger different forms of ER stress-mediated cell death, necroptosis, ferroptosis, pyroptosis, and apoptosis, and covers the underlying molecular basis of toxicant-induced ER stress, as well as potential target molecules.

Keywords

Acknowledgement

This research was supported by the National Research Foundation (NRF) grant funded by the Korea government (NRF2022R1A6A3A01086695 to JHT; NRF-2021R1A2B5B03086265 to SGK).

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