Modulation of the interaction between ROS, NO and CO by changes of intracellular redox status

다국어 초록 (Multilingual Abstract)

Aerobic cells can survive under constant oxidative stress by utilizing the intracellular redox buffer system. In aerobic cells, this redox buffer system is maintained by reversible oxidation and reduction of thiols. Transfer of electrons required for maintenance of redox buffer capacity is provided by nutrients and this is catalyzed by many antioxidant enzymes. For aerobic cells, most of the oxidative stimuli encountered at the cell membrane are translated and transduced into the cell by generation of reactive oxygen species(ROS) and this is catalyzed by the heme containing enzymes localized both at plasma membrane and mitochondria. The ROS, in turn, reacts with intracellular signal proteins and enzymes and alters their functions either directly by affecting the structures of these proteins or indirectly by decreasing the intracellular redox buffer capacity. In an effort to survive the stimuli, the oxidatively stressed cells then respond by inducing many enzymes which produce antioxidants like the GSH(glutathione reductase), NO(iNOS), prostaglandin(COX-2) or that inhibit excessive production of ROS and NO by degrading the heme contained in these enzymes(HO-1).
NO radical is a small lipid-soluble gas and is produced excessively by the iNOS, a heme containing enzyme induced in the stimulated macrophages. This NO reacts rapidly with ROS and neutralizes the toxicity of ROS as long as the intracellular buffering capacity(GSH) can be maintained. Prostaglandins(PGE2) generated upon induction of COX-2(another stress inducible heme enzyme) can dilate blood vessels to enhance delivery of oxygen and nutrients to the oxidatively stressed tissues. Alternatively, the oxidatively stressed cells can also respond to limit additional production of ROS, NO and PGE2 by inducing HO-1. HO-1 degrades the heme moiety contained in the enzymes producing ROS, NO and PGE2 and also generates CO that interferes the oxidative electron transfer catalyzed by these heme containing enzymes. The induction of these heme containing enzymes as well as the HO-1 in the oxidatively stressed cells is regulated by the intracellular redox status. Results supporting the interactive modulation of ROS, NO and CO production by changes of intracellular redox status will be discussed.