Silver nanoparticle-induced phosphorylation of histone H3 at serine 10 is due to dynamic changes in actin filaments and the activation of Aurora kinases

The phosphorylation of histone H3 at serine 10 (p-H3S10) has been closely correlated with mitotic chromosome condensation. We previously reported that silver nanoparticles (AgNPs) significantly induced p-H3S10 independent of mitosis. In the present study, we examined the mechanisms underlying the induction of p-H3S10 by AgNPs. A treatment with AgNPs markedly induced p-H3S10 in a dose-dependent manner in three types of cell lines, and this was dependent on the cellular incorporation of AgNPs. The immunofluorescent staining of AgNP-induced p-H3S10 was thin and solid throughout the nucleus, and differed from that normally associated with mitosis. AgNPs induced the formation of globular actin in a dose-dependent manner. Latrunculin B (LatB) and phalloidin, inhibitors of actin polymerization and depolymerization, respectively, inhibited p-H3S10, suggesting that dynamic changes in actin filaments are related to AgNP-induced p-H3S10. Furthermore, p-H3S10 was mediated by Aurora kinase (AURK) pathways, which were suppressed by LatB and siRNA for cofilin 1, an actin-depolymerizing protein. AgNO3 (Ag ions) exerted similar effects to those of AgNPs. These results suggest that Ag ions released from AgNPs incorporated into inner cells changed the dynamics of actin filaments, and this was followed by the activation of AURKs, leading to the induction of p-H3S10.