Molecular Mechanisms of Cadmium-Induced Apoptosis in Fish Cells: A Review

Abstract

Cadmium (Cd) is a typical heavy metal pollutant in aquatic environments. It enters fish through the gills, digestive tract, and body surface, and accumulates mainly in the liver and kidneys, with species- and tissue-specific distribution. Cadmium triggers apoptosis by inducing oxidative stress, calcium imbalance, and DNA damage. These signals are integrated and amplified by the mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, ultimately activating three downstream apoptotic execution pathways: the death receptor, mitochondrial, and endoplasmic reticulum stress pathways. These three pathways form an interactive network through molecular nodes such as BH3 interacting domain death agonist (Bid), Ca2+, c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP), synergistically amplifying the apoptotic effect, with the mitochondrial pathway playing a central role. Cadmium-induced apoptosis is dose-dependent: low concentrations activate protective responses, whereas high concentrations strongly promote apoptosis. Current research gaps remain regarding dynamic pathway crosstalk, chronic low-dose effects, species differences, and fish-specific apoptotic molecules (e.g., caspase-12 homologs). Future studies should focus on constructing multidimensional response maps, clarifying pathway activation thresholds and interaction contributions, and developing composite protective strategies based on Nrf2 activators, metal chelators, and antioxidants, thereby promoting translation into ecological risk assessment and aquaculture pollution control.