Ancient origins of nitric oxide signaling in biological systems

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Abstract
The simple gas nitric oxide (NO) controls a variety of complex biological processes, including blood pressure homeostasis, platelet aggregation, and transmission of signals by the nervous system. NO is also important for immune system function, playing key roles in the activation of macrophages and cellular defenses against microbial pathogens. Recent studies have revealed that some responses to NO are similar to those among very distantly related organisms; these findings suggest that many of the biological functions of NO have an evolutionarily ancient origin. This session addressed NO function in animals, microorganisms, and plants. Some effects of NO in animals are mediated by interactions with hemoglobin (Hb) that facilitate the delivery of oxygen to tissues with low oxygen tension. Interactions between NO and Hb have also been observed in bacteria, where they serve an alternative function in protecting bacteria from nitrosative stresses in their environment. Similarities between the mechanisms that control responses to pathogen attack in plants and innate immunity in animals led to a search for a role of NO in plant defense. This search has now borne fruit. Hb and NO have been inextricably linked from the earliest studies of globin function (1) to the recent identification of NO with biological activity (2). The standard model of Hb interaction with NO is based on two reactions, addition (or nitrosylation) and oxidation, expressed in Eqs. 1 and 2, respectively, below. 1 2 Both of these reactions were thought to be effectively irreversible. It was recently shown, however, that nitrosylHb is not stable at physiological ratios of NO to Hb—i.e., when NO:Hb ≪ 1. Rather, it is redox active—liberating NO− in the deoxy or T structure to form N2O (Eq. 3), and transferring NO+ to cysteine β93 within the R structure to form S-nitrosoHb (Eq. 4 …

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