Aflatoxin B1 exposure triggers inflammation and premature skin aging via ERMCS/Ca2+/ROS signaling cascade

Abstract

Aflatoxin B1 (AFB1) is a recognized hazard environmental contaminant mainly found in cereal and fruits. The toxicity of AFB1 exposure to various organs has been revealed in some literature. In current study, we explored the effect of AFB1 exposure on premature aging/senescence of skin. In vivo, 8-week-old C57 mice were used as models to evaluate the effect of dietary AFB1 exposure on premature skin aging. The results showed that AFB1 exposure caused premature skin aging by testing aging markers. Additionally, AFB1 led to oxidative stress and inflammatory response. In vitro, AFB1 exposure triggered premature cellular senescence in mouse skin fibroblasts cells (L929 cells) by assessing a range of cellular senescence-related markers. Further, the potential molecular mechanism by which AFB1 induce the premature skin aging was studied. ROS and Ca2+ is proven to be the key molecules in AFB1-induced cellular senescence. Further, through eliminating Ca2+, AFB1-caused oxidative stress and cellular senescence were both attenuated, suggesting that Ca2+ overload in the mitochondria results in cellular senescence by increasing ROS production. Next, we analyzed the causes of Ca2+ overload, and results showed that AFB1 exposure induces Ca2+ overload through increasing the formation of mitoguardin (Miga) and vesicle-associated membrane protein (VAMP)-associated protein (Vap33)-mediated endoplasmic reticulum (ER)–mitochondria contact sites (ERMCS). AFB1 exposure also inhibited mitophagy, leading to accelerate L929 cell senescence. In short, combining in vivo and in vitro results, we demonstrate that exposure to AFB1 causes premature skin aging, which is dependent on ERMCS/Ca2+/ROS/ signaling axis. The current study suggests that prolonged exposure to AFB1 makes skin more vulnerable to damage.