Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM_2.5) 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 <i>in vivo</i> assay system of <i>Caenorhabditis elegans</i>. 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 (<i>mtl-1</i> and <i>mtl-2</i>) encoded metallothioneins in the intestine. Mutation of the <i>mtl-1</i> or <i>mtl-2</i> gene resulted in a susceptible property of nematodes to outdoor PM_2.5 toxicity. Genetic assays suggested that <i>mtl-1</i> and <i>mtl-2</i> genes acted downstream of the <i>daf-16</i> gene encoding a FOXO transcriptional factor and <i>daf-2</i> 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.