Biotoxicity of paraquat to lung cells mediated by endoplasmic reticulum-mitochondria interactionMitochondrial dysfunction exposure mediates paraquat biotoxicity to lung tissue cells: The role of endoplasmic reticulum stress

Abstract

Abstract Paraquat (PQ) has attracted much attention in public and human health due to its high toxicity and lethality. Apoptosis is one of the numerous biotoxin mechanisms of action of PQ, which was confirmed in our previous study with increased fibrosis of lung tissue induced by ferroptosis.However, the understanding of the mechanism of PQ-induced apoptosis from the perspective of organelles, especially inter-organelle interactions, is still scarce. In this study, we observed that a certain dose of PQ gavage induced oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress in rat lung tissue cells.Western blot and quantitative real-time PCR showed that PQ toxicity activated the expression of Bcl-2 on the outer mitochondrial membrane and inhibited the expression of Bax. Bcl-2 increased the permeability of the mitochondrial membrane and led to the release of a number of apoptotic factors, thereby inducing endoplasmic reticulum stress and apoptotic cell death. CHOP produced by endoplasmic reticulum stress also regulates Bcl-2 expression, triggering mitochondria-endoplasmic reticulum interactions that mediate biotoxicity. In addition, 10 differential proteins were screened and validated by proteomics that may act as upstream and downstream active factors of mitochondria-endoplasmic reticulum interaction-mediated biotoxicity. Our findings provide new perspectives for researchers to explore the toxicity mechanisms of PQ to reduce their adverse effects.