Silver nanoparticle-induced hormesis of astroglioma cells: A Mu-2-related death-inducing protein-orchestrated modus operandi.

Hormesis is a dose-response phenomenon that, when applied to nanomaterial-biological interactions, refers to growth stimulation at low doses and growth inhibition at high doses. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. Astrocytes, the major glial cell type in the central nervous system, are a major source of brain tumors. In this study, we investigated whether silver nanoparticles (AgNPs) induce hormesis in astroglioma cells and the possible involvement of MuD in AgNP-induced hormesis. AgNPs exhibited cytotoxic effects on cell proliferation in a dose-dependent manner and increased MuD expression was observed during AgNP-induced astroglioma hormesis. Studies using MuD-knockout cells and MuD siRNA transfection showed that MuD might influence cell viability upon AgNP treatment. In addition, apoptotic cell population and production of reactive oxygen species in the absence of MuD were significantly increased. The phosphorylation of two mitogen-activated protein kinases, p38 and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinases (JNK), was observed upon AgNP stimulation. In summary, AgNPs at low doses induced hormesis of human astroglioma cells, and MuD and p38/ERK mediators are involved in AgNP-induced astroglioma hormesis, resulting in beneficial effects from the cellular point of view.