Oxidative Stress and Redox Modifications in Nanomaterial–Cellular Interactions

Abstract

The rapidly increasing development of engineered nanomaterials (ENMs) for multiple industries and societal applications has raised concern over the increased potential for human exposures. While knowledge gaps still exist regarding the fundamental mechanisms by which biological systems interact with and respond to various ENMs, it is now well established that many ENMs stimulate reactive oxygen species (ROS), either through direct redox chemistry or indirectly by modulating endogenous cellular metabolism. Indeed, many of the reported adverse biological responses to ENMs, such as the activation of antioxidant defense systems, inflammation, endoplasmic reticulum (ER) stress responses, and cell death, involve oxidative stress as a key event. Here, we summarize recent findings that support the central role of oxidative stress in ENM–cellular interactions, with an emphasis on phagocytic cells as an important target immune cell type. Emerging evidence enabled by new proteomics-based technologies indicates that redox-mediated cellular response pathways triggered by many ENMs may be initiated through the selective formation of protein redox modifications. The postulated role of protein redox modifications as molecular initiating events represents a novel conceptual framework for understanding specificity in ENM-induced oxidative stress responses and for discerning differences between cellular adaptive signaling and early toxicity.