Effect of Cu and Fe PM components on mitochondrial dynamics in human colon CaCo-2 cells

Abstract

Abstract Atmospheric particulate matter (PM) is one of the most dangerous air pollutants of anthropogenic origin; it consists of a heterogeneous mixture of inorganic and organic components, including transition metals and polycyclic aromatic hydrocarbons. Although previous studies have been focused on effect of exposure to highly concentrated PM on respiratory and cardiovascular systems, emerging evidence supports a significant impact of air pollution on gastrointestinal (GI) tract connecting the exposure to outdoor stressors with conditions such as appendicitis, colorectal cancer, and inflammatory bowel disease. In general, it has been postulated that the main mechanism involved in PM toxicity consists in an OxInflammatory response and this has been also suggested for the GI tract. In the present study we want to analyze the effect of specific redox-active PM components, such as copper (Cu) and iron (Fe), in human intestinal cells by focusing on ultrastructural integrity, redox homeostasis and modulation of some markers related to mitochondria dynamics. According to our study in CaCo2 cells, the exposure to the Cu- and Fe-PM components and their combination induced ultrastructural alterations in the endoplasmic reticulum with an additive effect when the cells were exposed to both PM (Cu and Fe). In addition, the expression and the protein levels of genes involved in mitochondria dynamic were clearly affected by the exposure. In particular, Mitofusin 1 and OPA1 increased after the single exposure and the combination of both particles showed an additive effect. Opposite trend was noticed for PINK and PARKIN. In general, our data suggest that acute exposure to specific Cu and Fe metals, can induce morphological and molecular damage in CaCo-2 cells confirming the correlation noticed between living in polluted area and incidence of gastrointestinal tract conditions.