Nickel nanoparticles induce autophagy and apoptosis via HIF-1α/mTOR signaling in human bronchial epithelial cells

Abstract

With the rapid development of nanotechnology, the potential adverse health effects of nanoparticles have been caught more attention and become global concerns. However, the underlying mechanisms in metal nanoparticle-induced toxic effects are still largely obscure. In this study, we investigated whether exposure to nickel nanoparticles (Nano-Ni) and titanium dioxide nanoparticles (Nano-TiO₂) would alter autophagy and apoptosis levels in normal human bronchial epithelial BEAS-2B cells and the underlying mechanisms involved in this process. Our results showed that the expressions of autophagy- and apoptosis-associated proteins were dysregulated in cells exposed to Nano-Ni. However, exposure to the same doses of Nano-TiO₂ had no significant effects on these proteins. In addition, exposure to Nano-Ni, but not Nano-TiO₂, led to nuclear accumulation of HIF-1α and decreased phosphorylation of mTOR in BEAS-2B cells. Inhibition of HIF-1α by CAY10585 abolished Nano-Ni-induced decreased phosphorylation of mTOR, while activation of mTOR by MHY1485 did not affect Nano-Ni-induced nuclear accumulation of HIF-1α. Furthermore, both HIF-1α inhibition and mTOR activation abolished Nano-Ni-induced autophagy but enhanced Nano-Ni-induced apoptosis. Blockage of autophagic flux by Bafilomycin A1 exacerbated Nano-Ni-induced apoptosis, while activation of autophagy by Rapamycin effectively rescued Nano-Ni-induced apoptosis. In conclusion, our results demonstrated that Nano-Ni exposure caused increased levels of autophagy and apoptosis via the HIF-1α/mTOR signaling axis. Nano-Ni-induced autophagy has a protective role against Nano-Ni-induced apoptosis. These findings provide us with further insight into Nano-Ni-induced toxicity.

Keywords: Apoptosis; Autophagy; HIF-1α; Nickel nanoparticles; mTOR.