Molecular mechanisms of lead-induced changes of selenium status in mice livers through interacting with selenoprotein P

Abstract

As a heavy metal generally considered to be toxic, lead displays the destruction of the antioxidant system and causes oxidative damage through animal, cellular and molecular evidences. Selenium exists in the form of selenocysteine (Sec) upon its incorporation into selenoproteins and plays vital roles in protection from oxidative stress caused by toxic materials such as lead. This study investigated mechanisms of lead-induced changes of selenium status both at the animal and molecular levels. Total selenium concentrations in blood plasma, contents of glutathione peroxidase 3 (Gpx3) and selenoprotein P (SelP) in blood plasma and mRNA levels of key selenoproteins in mice livers were significantly inhibited after lead exposure, and indicators of oxidative damages in mice livers caused by lead also presented significantly higher, including levels of reactive oxygen species, malonaldehyde concentration and TNF-α levels. To further confirm the hypothesis that lead may disturb selenium status through affecting SelP function, we investigated molecular mechanisms of lead on SelP in vitro. Results indicated that lead changed secondary structure of SelP by loosening and destruction its skeleton. This work presents molecular mechanisms changes of selenium status in mice livers caused by lead combined in vivo and in vitro studies, and contributes to a better understanding of lead toxicity on human health.