Involvement of the JNK/HO‑1/FTH1 signaling pathway in nanoplastic‑induced inflammation and ferroptosis of BV2 microglia cells

Abstract

Nanoplastics (NPs) are a newly discovered type of environmental pollutant. The potential for neurotoxicity caused by NPs and their mechanisms are unclear. The present study aimed to determine the molecular mechanism underlying neurotoxicity induced by NPs. Microglia (BV2) cells were used for in vitro studies, and it was found that NPs invaded cells, activated inflammasomes, induced the release of significant quantities of inflammatory factors by detection of inflammatory response-associated proteins through Western blot and ELISA. By detection of FITC, SOD, GSH, cellular iron level, and ferroptosis-related proteins, it was found that NPs compromised the anti-oxidative mechanisms of cells, increased intracellular lipid peroxidation and Fe 2+ concentration and triggered inflammatory reactions and ferroptosis. Pretreatment with reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) alleviated induction of inflammatory reactions and ferroptosis of cells. In addition, inhibiting expression of c-Jun N-terminal kinase (JNK) increased expression of heme oxygenase (HO-1), resulting in decreased ferroptosis, indicating that the JNK/HO-1 signaling pathway was involved in NP-induced effects on ferroptosis in BV2 cells. In conclusion, NPs could induce inflammatory responses and ferroptosis in BV2 cells. JNK/HO-1 mediated ferroptosis may serve an important role in the toxicity of microglia induced by NPs. This study provided novel evidence for the toxic effects of NPs and highlighted a theoretical mechanistic basis for safe prevention and treatment of plastic pollution-induced neurotoxicity.

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish

“…Its application has been instrumental in determining the significant role of ROS in cell apoptosis, ferroptosis pathways, and inflammatory response. Sun et al reported that NAC alleviated the inflammatory response and ferroptosis of BV2 microglia cells induced by PS-NPs ( Sun et al, 2023 ). Li et al (2023) found that mitochondrial damage, cell apoptosis, and oxidative stress in human liver HepG2 cells induced by PS-NPs were reversed by pretreatment of NAC.…”

Important Factors Affecting Induction of Cell Death, Oxidative Stress and DNA Damage by Nano- and Microplastic Particles In Vitro

“…The findings indicate that exposure to PS-NPs caused cell damage by ferroptosis (Figure 1). Sun et al [68] found that NPs of 44 nm in diameter entered microglial cells (BV2) and induced oxidative stress and inflammation reactions at 25-100 µg/mL. Based on ROS level, SOD activity and the levels of GSH, cell iron, and ferroptosis-related proteins, it was found that NPs compromised the antioxidative mechanisms of microglial (BV2) cells, increased intracellular lipid peroxidation and Fe 2+ concentration, triggering inflammation reactions and ferroptosis.…”