Working with nitric oxide and hydrogen sulfide in biological systems

Abstract

(H 2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were first known as environmental toxicants, it is now evident that that they are intricately involved in diverse cellular functions with impact on numerous physiological and pathogenic processes. NO and H 2S share some common characteristics but also have unique chemical properties that suggest potential complementary interactions between the two in affecting cellular biochemistry and metabolism. Central among these is the interactions between NO, H 2S, and thiols that constitute new ways to regulate protein function, signaling, and cellular responses. In this review, we discuss fundamental biochemical principals, molecular functions, measurement methods, and the pathophysiological relevance of NO and H 2S. thiol; oxidation; redox; pulmonary; cardiovascular HISTORICALLY CONSIDERED ONLY as industrial pollutants, nitric oxide (NO) and hydrogen sulfide (H 2 S) are now appreciated as two key physiologically produced signaling molecules that control multiple cellular functions. Appreciation that dysfunction in how these solvated gases affect these functions, through either deficient formation or downstream reactivity, has opened up new therapeutic avenues for a host of diseases in all major organ systems including the lung. Our understanding of NO homeostasis mechanisms are relatively advanced compared with H 2 S, primarily because of the latter's discovery as a biologically relevant entity being postdated by a decade or more compared with NO. Although they are chemically distinct, there are intriguing parallel mechanisms/concepts in NO and H 2 S biology that include overlapping functions, technical challenges in how each of these gases are measured in biological milieu, appreciation of the mechanisms and factors that modulate how metabolism of each of these is regulated, and therapeutic potential for either inhibiting or repleting NO or H 2 S. In this article, and within the framework outlined above, we provide a general overview of NO and H 2 S biology. Nitric Oxide Formation: Enzymatic and Nonenzymatic SourcesEnzymatic sources. Nitric oxide is synthesized by one of three different isoforms of nitric oxide synthase (NOS) that differ in enzymatic activity, in how they are regulated (transcriptional, translational, and posttranslational mechanisms), and in how they are expressed/compartmentalized in tissues as well as the subcellular level. These are called NOS I, II, and III, corresponding to the inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) isoforms, typically with high, mid, and low activities, respectively. In the systemic and pulmonary vasculature, eNOS plays a key role in controlling blood flow and maintaining an antithrombotic and anti-inflammatory luminal surface. On the other hand, iNOS is induced by inflammatory stimuli in leukocytes, airway epithelial cells, and alveolar macrophages to mediate pathogen killing. However, production of NO at higher concentrations in ...

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

“…As such, sulfide salts are poor models for determining the role of endogenous H 2 S in physiological systems or exploring the pharmacological and therapeutic potential of H 2 S-donating molecules. Although several detailed and excellent reviews have explicitly highlighted how Na 2 S and NaSH should and should not be used Yuan et al 2015;Hughes et al 2009;Olson 2013) in the laboratory (e.g. preparing and storing solutions, effects of pH and buffers, preventing loss of H 2 S to the atmosphere, etc.…”

Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats

“…the electrically-induced neurotransmitter release) was estimated indirectly by measurement of the electrically induced vasopressor response; and (2) in aqueous solution, H 2 S is dissociated and depending of the preparation, it is estimated that one-third is H 2 S, while two-third is HS -with negligible amounts of S 2 À (Yuan et al, 2015).…”

Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide

“…Although several detailed and excellent reviews have explicitly highlighted how Na 2 S and NaSH should and should not be used Yuan et al 2015;Hughes et al 2009; in the laboratory (e.g. preparing and storing solutions, effects of pH and buffers, preventing loss of H 2 S to the atmosphere, etc.…”