Carbon Monoxide (CO), Nitric Oxide, and Hydrogen Sulfide Signaling During Acute CO Poisoning

Abstract

Major toxic effects of acute carbon monoxide (CO) poisoning result from increases in reactive oxygen species (ROS) and reactive nitrogen species (RNS) producing oxidative stress. The importance of altered nitric oxide (NO) signaling in evoking increases in RNS during CO poisoning has been established. Although there is extensive literature describing NO and hydrogen sulfide (H₂S) signaling in different types of cells under normal conditions, how CO poisoning-evoked deregulation of additional NO signaling pathways and H₂S signaling pathways could result in cell injury has not been previously considered in detail. The goal of this article was to do this. The approach was to use published data to describe signaling pathways driven by CO bonding to different ferroproteins and then to collate data that describe NO and H₂S signaling pathways that could interact with CO signaling pathways and be important during CO poisoning. Arteriolar smooth muscle cells-endothelial cells located in the coronary and some cerebral circulations-were used as a model to illustrate major signaling pathways driven by CO bonding to different ferroproteins. The results were consistent with the concept that multiple deregulated and interacting NO and H₂S signaling pathways can be involved in producing cell injury evoked during acute CO poisoning and that these pathways interact with CO signaling pathways.

Keywords: carbon monoxide poisoning; carbon monoxide signaling; gaso-transmitters; hydrogen sulfide signaling; nitric oxide signaling; redox signaling.

FIGURE 1

Possible interactions between CO, NO, and H₂S signaling pathways in an arteriolar SMCs-ECs model. The schema drawn above the dotted line indicates intracellular reactions (within SMCs and ECs). Below the interrupted line are the events in blood in the coronary or cerebral circulations. Because the goal of this article was to highlight effects of CO bonding with FPs, this is depicted as a central circle. FPs considered here are described in the text. Arrows illustrate the different signaling pathways possibly involved in CO poisoning-evoked cell injury. The various signaling pathways are described in the text. Abbreviations: CO, carbon monoxide; NO, nitric oxide; H₂S, hydrogen sulfide; ROS, reactive oxygen species; RNS, reactive nitrogen species; M–BFC–metabolism, blood flow coupling; HIF-1α, hypoxia-induced factor-1α; PcO₂, mean capillary PO₂; ROS Scav, ROS scavengers.