Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM2.5) during Spring Festival in Beijing in nematode Caenorhabditis elegans

Abstract

In this study, we performed the toxicological assessment of outdoor PM_2.5 collected from Beijing during Spring Festival using the in vivo assay system of Caenorhabditis elegans. Acute exposure to outdoor PM_2.5 at a concentration of 10 mg L⁻¹ and prolonged exposure to outdoor PM_2.5 at concentrations of 0.1–10 mg L⁻¹ decreased locomotion behavior and caused significant induction of intestinal ROS production. Meanwhile, outdoor PM_2.5 exposure induced significant expression of gene (mtl-1 and mtl-2) encoded metallothioneins in the intestine. Mutation of the mtl-1 or mtl-2 gene resulted in a susceptible property of nematodes to outdoor PM_2.5 toxicity. Genetic assays suggested that mtl-1 and mtl-2 genes acted downstream of the daf-16 gene encoding a FOXO transcriptional factor and daf-2 gene encoding an insulin receptor in the insulin signaling pathway to regulate outdoor PM_2.5 toxicity. DAF-2 further acted upstream of DAF-16 and suppressed the function of DAF-16 to regulate outdoor PM_2.5 toxicity. Therefore, we identified a signaling cascade of DAF-2-DAF-16-MTL-1/2 in the control of outdoor PM_2.5 toxicity in nematodes. Our study provides an important molecular basis for the potential toxicity of outdoor PM_2.5 during Spring Festival in Beijing in nematodes. Especially, our study will highlight the potential adverse effects of outdoor PM_2.5 during Spring Festival on environmental organisms.