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ROS-mediated PERK-CHOP pathway plays an important role in cadmium-induced HepG2 cells apoptosis
Cao Zhaohui1,2, Tang Cifei1,2, Huang Di1,2
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, China.
Environmental Toxicology
|June 10, 2023
Summary
Cadmium exposure causes liver cell death by inducing oxidative and endoplasmic reticulum stress, activating a specific apoptotic pathway. Targeting these stresses may offer new therapeutic strategies for cadmium-induced liver damage.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Cadmium (Cd) is a toxic heavy metal with known liver toxicity.
- The precise mechanisms of Cd-induced hepatotoxicity and apoptosis remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which Cd induces apoptosis in HepG2 liver cells.
- To investigate the roles of oxidative stress and endoplasmic reticulum (ER) stress in Cd-induced hepatotoxicity.
Main Methods:
- HepG2 cells were exposed to Cadmium.
- Cell viability, apoptosis, reactive oxygen species (ROS) levels, and ER stress markers (PERK, CHOP, Ca2+ release) were assessed.
- N-acetyl-l-cysteine (NAC) was used as a ROS scavenger.
Main Results:
- Cd exposure significantly reduced HepG2 cell viability and increased apoptosis.
- Cd induced oxidative stress by increasing ROS levels and ER stress via the PERK-CHOP pathway.
- NAC pretreatment attenuated ER stress and protected ER function, indicating a link between oxidative and ER stress.
Conclusions:
- Cd induces HepG2 cell death through a ROS-mediated apoptotic pathway involving ER stress (PERK-CHOP axis).
- This study reveals a novel mechanism of Cd-induced hepatotoxicity.
- Inhibitors of oxidative and ER stress may represent a therapeutic approach for Cd-induced liver injury.
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