Effect of Cu- and Fe- Isolated from Environmental Particulate Matter on Mitochondrial Dynamics in Human Colon CaCo-2 Cells.

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 focused on the effects of exposure to highly concentrated PM on the respiratory and cardiovascular systems, emerging evidence supports a significant impact of air pollution on the gastrointestinal (GI) tract by linking exposure to external stressors with conditions such as appendicitis, colorectal cancer, and inflammatory bowel disease. In general, it has been hypothesized that the main mechanism involved in PM toxicity consists of an inflammatory response and this has also been suggested for the GI tract. In the present study, we analyzed the effect of specific redox-active PM components, such as copper (Cu) and iron (Fe), in human intestinal cells focusing on ultrastructural integrity, redox homeostasis, and modulation of some mitochondrial-related markers. According to our results, exposure to Cu- and Fe-PM components and their combination induced ultrastructural alterations in the endoplasmic reticulum and in the mitochondria with an additive effect when combined. The increase in ROS and the loss of the mitochondrial mass in the cells exposed to PM indicates that mitochondria are a target of acute metal exposure. Furthermore, the gene expression and the protein levels of mitochondria dynamics markers were affected by the PM exposure. In particular, OPA1 increases at both gene and protein levels in all conditions while Mitofusin1 decreases significantly only in the presence of Fe. The increase in PINK expression is modulated by Fe, while Cu seems to affect mainly Parkin. Finally, a significant decrease in trans-epithelial resistance was also observed. In general, our study can confirm the correlation observed between pollution exposure areas and increased incidence of GI tract conditions.