Ambient carbon nanoparticles activated Nrf2 signaling through adsorbed iron or quinones

Evidence indicates that oxidative stress plays a central role in the pathogenesis of harmful effects caused by airborne nanoparticle (ANP), a health hazard associated with various diseases. Carbon nanoparticles are a major component of urban ANP, and usually adsorbs transition metals especially iron and organics on the surface. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a major transcription factor that is activated and regulates the induction of a series of antioxidant and detoxification genes upon oxidative stress. How Nrf2-regulated protective mechanism responds to the exposure of different forms of carbon nanoparticle is largely unclear. Here we examined the activation of Nrf2 signaling in human macrophages in response to carbon nanoparticles (CNP, 20-50 nm in diameter)), and CNP-doped with iron (CNP-Fe) or 1,4-naphthoquinone (CNP-Q). In contrast to ANP collected from urban area and CNP-Q, neither CNP nor CNP-Fe increased H 2 O 2 level in macrophages. However CNP-Fe (but not CNP and CNP-Q) increased lipid peroxidation. Nrf2 nuclear translocation (marker of Nrf2 activation) was increased in response to exposure of CNP-Fe and CNP/Q, but not by CNP. Consistently, the mRNA expression of Nrf2-regulated genes (GCLC, GCLM, HO-1, and NQO1) was significantly induced by CNP-Fe and CNP/Q, but not by CNP. In summary, these data demonstrated that iron and quinones adsorbed on the surface of carbon nanoparticle were involved in the Nrf2 activation, but that the mechanisms likely differ.