Hydrogen Sulfide in Renal Physiology and Disease

Abstract

Significance: Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease.

Critical issues: H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum-induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells.

Future directions: Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731.

Keywords: acute kidney injury; chronic kidney disease; diabetic kidney disease; hypertension; renal physiology.

FIG. 1.

H2S synthesis. H2S, hydrogen sulfide; CBS, cystathionine β-synthase; CSE, cystathione γ-lyase; 3-MST, 3-mercaptopyruvate sulfurtransferase; AAT, aspartate aminotransferase; DAO, D-amino acid oxidase.

FIG. 2.

Modification of proteins by sulfhydration.

FIG. 3.

Signaling pathways involved in H2S amelioration of high glucose-induced protein synthesis. NaHS, sodium H2S; CaMKKβ, Ca(2+)/calmodulin-dependent protein kinase kinaseβ; LKB1, liver kinase B1; AMPK, AMP-activated protein kinase; mTOR, mechanistic target of rapamycin; eIF4E, eukaryotic initiation factor 4E; 4E-BP1, eIF4E-binding protein 1; eIF4A, eukaryotic initiation factor 4A; eIF4G, eukaryotic initiation factor 4G; PDCD4, programmed cell death protein 4; p70S6K, p70 S6 kinase; eEF2, eukaryotic elongation factor 2; eEF2K, eEF2 kinase.

FIG. 4.

Signaling pathways activated by H2S in renal cells. (A) Signaling pathways involved in H2S amelioration of high glucose-induced renal extracellular matrix increment in kidney cells. (B) Signaling pathways involved in tadalafil (a phosphodiesterase-5 inhibitor)-induced amelioration of high glucose-induced renal extracellular matrix increment in kidney cells. iNOS, inducible nitric oxide synthase; NO, nitric oxide; Nox4, NADPH oxidase 4; mTORC1, mechanistic target of rapamycin complex 1.