Dataset Information

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 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.

SUBMITTER: Yang R

PROVIDER: S-EPMC6060693 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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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.

Yang Ruilong R Rui Qi Q Kong Ling L Zhang Nan N Li Yu Y Wang Xinyu X Tao Jing J Tian Peiyao P Ma Yan Y Wei Jianrong J Li Guojun G Wang Dayong D

Toxicology research 20160418 4

In this study, we performed the toxicological assessment of outdoor PM2.5 collected from Beijing during Spring Festival using the in vivo assay system of Caenorhabditis elegans. Acute exposure to outdoor PM2.5 at a concentration of 10 mg L-1 and prolonged exposure to outdoor PM2.5 at concentrations of 0.1-10 mg L-1 decreased locomotion behavior and caused significant induction of intestinal ROS production. Meanwhile, outdoor PM ...[more]

PMID: 30090415

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Project description:Epidemiological studies have consistently linked exposure to PM2.5 with adverse health effects. The oxidative potential (OP) of aerosol particles has been widely suggested as a measure of their potential toxicity. Several acellular chemical assays are now readily employed to measure OP; however, uncertainty remains regarding the atmospheric conditions and specific chemical components of PM2.5 that drive OP. A limited number of studies have simultaneously utilised multiple OP assays with a wide range of concurrent measurements and investigated the seasonality of PM2.5 OP. In this work, filter samples were collected in winter 2016 and summer 2017 during the atmospheric pollution and human health in a Chinese megacity campaign (APHH-Beijing), and PM2.5 OP was analysed using four acellular methods: ascorbic acid (AA), dithiothreitol (DTT), 2,7-dichlorofluorescin/hydrogen peroxidase (DCFH) and electron paramagnetic resonance spectroscopy (EPR). Each assay reflects different oxidising properties of PM2.5, including particle-bound reactive oxygen species (DCFH), superoxide radical production (EPR) and catalytic redox chemistry (DTT/AA), and a combination of these four assays provided a detailed overall picture of the oxidising properties of PM2.5 at a central site in Beijing. Positive correlations of OP (normalised per volume of air) of all four assays with overall PM2.5 mass were observed, with stronger correlations in winter compared to summer. In contrast, when OP assay values were normalised for particle mass, days with higher PM2.5 mass concentrations (μgm-3) were found to have lower mass-normalised OP values as measured by AA and DTT. This finding supports that total PM2.5 mass concentrations alone may not always be the best indicator for particle toxicity. Univariate analysis of OP values and an extensive range of additional measurements, 107 in total, including PM2.5 composition, gas-phase composition and meteorological data, provided detailed insight into the chemical components and atmospheric processes that determine PM2.5 OP variability. Multivariate statistical analyses highlighted associations of OP assay responses with varying chemical components in PM2.5 for both mass- and volume-normalised data. AA and DTT assays were well predicted by a small set of measurements in multiple linear regression (MLR) models and indicated fossil fuel combustion, vehicle emissions and biogenic secondary organic aerosol (SOA) as influential particle sources in the assay response. Mass MLR models of OP associated with compositional source profiles predicted OP almost as well as volume MLR models, illustrating the influence of mass composition on both particle-level OP and total volume OP. Univariate and multivariate analysis showed that different assays cover different chemical spaces, and through comparison of mass- and volume-normalised data we demonstrate that mass-normalised OP provides a more nuanced picture of compositional drivers and sources of OP compared to volume-normalised analysis. This study constitutes one of the most extensive and comprehensive composition datasets currently available and provides a unique opportunity to explore chemical variations in PM2.5 and how they affect both PM2.5 OP and the concentrations of particle-bound reactive oxygen species.

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Dataset Information

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.

Publications

Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM<sub>2.5</sub>) during Spring Festival in Beijing in nematode <i>Caenorhabditis elegans</i>.

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