The Role of Nitric Oxide in the Regulation of Cellular Iron Metabolism

Eukaryotic cellular iron homeostasis becomes impaired during inflammation, manifesting itself most dramatically as the anemia of chronic disease. This alteration in cellular iron metabolism is the result of a complex network of events, acting at the transciptional and translational levels to alter the expression of proteins involved in the uptake, storage, and utilization of iron. With the discovery of nitric oxide (NO), its role in host defense, and its interactions with a number of different iron-containing proteins, investigators have begun unravelling the connection between iron metabolism and NO. Following a brief discussion of normal cellular iron metabolism, this review focuses on alterations in iron homeostasis observed during inflammation with an emphasis on the role of NO. A working model involving NO in the pathogenesis of the anemia of chronic disease is proposed.