Redox-Dependent Regulation of the Expression of Nitric Oxide-Inducible Genes

Nitric oxide (NO) is a mobile, highly reactive signal molecule, and changes the expression of specific genes in effector cells. Under physiological conditions, NO reacts with molecular oxygen and reactive oxygen species (ROS) to produce intermediates known as reactive nitrogen species (RNS). The production of NO and RNS in the cell is controlled by hormones, neurotransmitters, cytokines, and growth factors. Hence NO and its derivatives act as secondary paracrine factors and transmit the signal from NO-producing to neighboring cells. Intracellular reception of NO and RNS is due to Src-related tyrosine protein kinases, G-protein Ras, cytochrome oxidase, and guanylate cyclase. Receptor proteins mostly contain heme, active thiol, or iron–sulfur groups, and are both on the plasma membrane and in internal cell compartments. Many of the NO receptors are key components of cell regulatory systems controlling the transcription factors AP-1, HIF-1, NF-κB, and p53 and the expression of their target genes. A distinguishing feature of NO signaling is that changes in the redox potential of the cell switch the NO receptor and, consequently, modify the NO effect. Depending on the ROS level, NO activates different signal transduction pathways to induce (or suppress) different gene sets. The data considered indicate that antioxidants may be used to directionally change the transcriptional response of the cell to NO.