The Role of Hydrogen Sulfide in Renal System

Abstract

Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H2S in mammalian renal system, with emphasis on both renal physiology and diseases. H2S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H2S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells. Likewise, it also influences the release of renin from juxtaglomerular cells and thereby modulates blood pressure. A possible role of H2S as an oxygen sensor has also been discussed, especially at renal medulla. Alternation of H2S level has been implicated in various pathological conditions such as renal ischemia/reperfusion, obstructive nephropathy, diabetic nephropathy, and hypertensive nephropathy. Moreover, H2S donors exhibit broad beneficial effects in renal diseases although a few conflicts need to be resolved. Further research reveals that multiple mechanisms are underlying the protective effects of H2S, including anti-inflammation, anti-oxidation, and anti-apoptosis. In the review, several research directions are also proposed including the role of mitochondrial H2S in renal diseases, H2S delivery to kidney by targeting D-amino acid oxidase/3-mercaptopyruvate sulfurtransferase (DAO/3-MST) pathway, effect of drug-like H2S donors in kidney diseases and understanding the molecular mechanism of H2S. The completion of the studies in these directions will not only improves our understanding of renal H2S functions but may also be critical to translate H2S to be a new therapy for renal diseases.

Tissue-dependent variations of hydrogen sulfide homeostasis in anoxic freshwater turtles

“…The enzyme D-amino acid oxidase constitutes an additional enzymatic pathway for H 2 S production and is highly expressed in mammalian kidneys (Shibuya et al, 2013). In mammals, endogenous H 2 S is proposed to be important for normal kidney function (Lobb et al, 2015) and H 2 S has been shown to increase glomerular filtration rate (Xia et al, 2009) and salt excretion by inhibition of Na + /K + -ATPase (Ge et al, 2014), and to suppress renin release (Cao and Bian, 2016). Given that H 2 S is an ancient vasoregulatory molecule across multiple vertebrate clades (Dombkowski et al, 2004), our data indicate that H 2 S could also have a similar regulatory role in the renal function of turtles.…”

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

“…However, recent publications have revealed that H 2 S is synthesized in mammalian tissues, and freely travels through cell membranes. H 2 S acts independently of any specific transporters, and it has a number of biological effects on various systems (Meng et al, ; Cao and Bian, ; Feliers et al, ; Ianaro et al, ; Katsouda et al, ; Cheng et al, ). Nowadays, H 2 S is regarded as the third endogenous gasotransmitter followed by NO and CO (Hine et al, ).…”

Hydrogen sulfide upregulates renal AQP‐2 protein expression and promotes urine concentration

“…Both CBS and CSE are critical for H 2 S generation in the kidney (5,12). Our data showed that the suppression of the endogenous H 2 S production by the inhibition of CBS and CSE in mice caused increased urine output, decreased urine osmolality, and impaired urine concentration in response to water deprivation.…”

“…CBS catalyzes homocysteine derived from methionine to produce cystathionine, which is converted into L-cysteine by CSE. L-Cysteine can be used as a substrate by both CBS and CSE to generate H 2 S. CSE can also catalyze H 2 S production by the conversion of homocysteine into homolanthionine (4,5), CBS is critical in the development of neonatal mice. Moribund CBS knockout (cbs 2/2 ) mice exhibit severe fibrosis and neutrophil invasion.…”