Brian Thrall, Ph.D.
Battelle Pacific Northwest Laboratories
An NIEHS grantee and colleagues have developed an analytic approach called quantitative redox proteomics that can detect how nanoparticles affect macrophages long before these immune cells die. Using this method, they found that even nanoparticles considered non-toxic can cause macrophages to experience some oxidative stress.
Many approaches to studying nanoparticle toxicity examine whether the particles cause cell death. The new quantitative redox proteomics approach provides more specific information by detecting proteome-wide S-glutathionylation. This modification, which occurs when a cell is under oxidative stress, is known to be involved in immune function. Using the new analysis technique, the researchers examined macrophages after exposure to silicon oxide, iron oxide, or cobalt oxide. These commercial nanoparticles vary in their potential to cause oxidative stress and cell death.
All three types of nanoparticles caused an increase in S-glutathionylation. However, the specific pattern of S-glutathionylation varied depending on the type of nanoparticle. By closely examining these modifications, the researchers identified specific molecular pathways that were most susceptible to low levels of oxidative stress and distinguished those from pathways associated with oxidative stress levels that were high enough to cause cell death. These findings offer insight into the pathways that may facilitate cellular adaption to nanoparticles versus pathways that linked to irreversible cell damage.
Citation: Duan J, Kodali VK, Gaffrey MJ, Guo J, Chu RK, Camp DG, Smith RD, Thrall BD, Qian WJ. 2015. Quantitative profiling of protein s-glutathionylation reveals redox-dependent regulation of macrophage function during nanoparticle-induced oxidative stress. ACS Nano. 10(1):524-538.