| dc.description.abstract | Abstract
Arsenic is a common environmental toxicant associated with human skin, lung and liver cancers. Recently, numerous studies suggested that arsenic-induced toxicity is associated with the generation of free radicals. To cope with the oxidative stress, the cell has developed various defense mechanism. Thioredoxin peroxidase II (TPx II) is an oxidative stress-inducible enzyme. TPx II functions in cell proliferation and differentiation, and protects other proteins from oxidative damage.
In this study, we investigate the effect of arsenic compounds on the expression of TPx II. The results showed that arsenite induces TPx II protein expression in SA7N cell (a revertant of arsenic resistant Chinese hamster ovary cells), but not in other cell lines such as H1299、H460、HFW、IRC、KB、HaCaT. Moreover, the induction of TPx II also accompanied with H2O2 accumulation in SA7N cells. We therefore further explore the signaling pathway involved in TPx II induction by arsenite in SA7N cells. The results showed that pre-treatment of SA7N cells with inhibitors of protein kinase A (PKA), extracellular-regulated kinase (ERK), p38 and tyrosine kinase had no effect on the induction of TPx-II expression by arsenite. Calcium chelators, such as EGTA and BAPTA/AM, also showed no effect on TPx-II induction by arsenite. However, arsenite-induced TPx-II expression was dose-dependently reduced by two broad–based protein kinase C (PKC) inhibitors, Rottlerin and Staurosprine. Furthermore, two highly specific inhibitors of PKCδ, Go6983 and Calphostin C ,
also decreased arsenite-induced TPx II expression. The present results suggested that PKCδ might be involved in arsenite-induced TPx II expression in SA7N cells. | en_US |