Physiological Role of Hydrogen Sulfide in the Renal System

Hydrogen sulfide (H2S), a gas with a characteristic rotten-egg smell, gained historic notoriety for its toxicity and death at high concentrations especially among industrial workers. This is due to its ability to reversibly inhibit the activity of cytochrome c oxidase, a terminal enzyme of the mitochondrial electron transport chain. Recently, however, H2S has risen above its notorious public image and is now seen by researchers as an endogenously produced gaseous signaling molecule that plays an important role in cellular homeostasis and influences several physiological and pathological processes at low physiological and non-toxic concentrations. Its production is catalyzed by two cytosolic enzymes, cystathionine β-synthase and cystathionine γ-lyase, a mitochondrial enzyme, 3-mecaptopyruvate sulfurtransferase, and a peroxisomal enzyme, d-amino acid oxidase. Several recent experimental studies have demonstrated that at low micromolar concentrations, H2S plays a complex and essential role in normal renal function, and dysregulation of its production has been implicated in various renal pathologies. In addition, exogenous H2S administration has been reported to exhibit important therapeutic characteristics that target multiple molecular pathways in common renal pathologies in which reduced levels of renal and plasma H2S were observed. This chapter presents current understanding of H2S in the physiology of the renal system, and lays the foundation for discussion on H2S as a novel pharmacological agent to modify organ transplantation protocol, which are discussed in the subsequent chapters of this book.