Epigenetic effects of silver nanoparticles and ionic silver in Tetrahymena thermophila

Highlights: • Ag⁺ and Ag NPs are both toxic to T. thermophila mainly via causing oxidative stress. • The toxicity of Ag NPs depends on their physicochemical properties. • LncRNA-mRNA cascade regulates T. thermophila's response to Ag⁺ and Ag NPs exposure. • T. thermophila activated antioxidant response via lncRNA-mRNA co-expression networks. The widespread use of silver nanoparticles (Ag NPs) has raised substantial health risks, but little is known about the epigenetic toxicity induced by Ag⁺ and Ag NPs. This study characterized physiological and lncRNA profiles to explore the toxic effects and epigenetic mechanisms in Tetrahymena thermophila on exposure to Ag⁺ (in the form of AgNO₃) and different Ag NPs for 24 h. The Ag NPs studied varied in size (10 nm and 80 nm) and surface coating (citrate and polyvinylpyrrolidone). We found that both Ag⁺ and Ag NPs elicited strong growth-inhibiting effects on T. thermophila. The toxicity was mainly caused by high reactive oxygen species (ROS) levels, leading to lipid peroxidation and mitochondrial dysfunction. To combat the oxidative stress, the protist activated an antioxidative response, increasing the activity of glutathione peroxidase and other antioxidants. Notably, 1250 lncRNAs were differentially expressed under Ag⁺ or Ag NPs exposure relative to the non-exposure control, which were clustered into 15 expression modules in weighted gene co-expression network analysis. These gene modules exhibited toxicant-specific expression patterns, potentially playing regulatory roles, via their co-expressed mRNAs, to inhibit cell growth, activate cell membrane cation channel, and promote oxidoreductase activity. This research illuminates how post-transcriptional mechanisms of a ciliated protozoan regulate responses to Ag⁺ and Ag NPs toxicities.