Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis

Figure 1

Sources of ROS and regulation cellular redox homeostasis in hematopoiesis. Ionizing radiation (IR), ultraviolet (UV), chemical drugs, etc. result in exogenous elevated ROS levels. Accumulated O2^- molecules by mitochondria and membrane NADPH oxidase (NOX) in cells are first converted by superoxide dismutase (SOD) into H₂O₂. H₂O₂ quickly converts into harmless water (H₂O) in the presence of catalase, glutathione (GSH), glutathione peroxidase (GPX), peroxiredoxin (PRX), and thioredoxin (TRX). If cells are insufficient to detoxify H₂O₂, the remaining H₂O₂ is converted into even more toxic OH^- ions. OH^- ions can lead to destruction of cellular macromolecules including proteins, nuclear acids, and lipids. N-acetyl cysteine (NAC) and resveratrol are two small molecule antioxidants which reduce ROS levels. In hematopoiesis, dormant, quiescent HSCs are characterized by low ROS levels. Elevated ROS levels in HSCs enhance cycling and promote differentiation and mobilization.