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Hydrogen sulfide (H2S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbon monoxide. Exogenous treatment with H2S can induce a reversible hypometabolic state, which can protect organs from ischemia/reperfusion injury, but whether cystathionine γ-lyase (CSE), which produces endogenous H2S, has similar protective effects is unknown. Here, human renal tissue revealed abundant expression of CSE, localized to glomeruli and the tubulointerstitium. Compared with wild-type mice, CSE knockout mice had markedly reduced renal production of H2S, and CSE deficiency associated with increased damage and mortality after renal ischemia/reperfusion injury. Treatment with exogenous H2S rescued CSE knockout mice from the injury and mortality associated with renal ischemia. In addition, overexpression of CSE in vitro reduced the amount of reactive oxygen species produced during stress. Last, the level of renal CSE mRNA at the time of organ procurement positively associated with GFR 14 days after transplantation. In summary, these results suggest that CSE protects against renal ischemia/reperfusion injury, likely by modulating oxidative stress through the production of H2S.

Original publication

DOI

10.1681/ASN.2012030268

Type

Journal article

Journal

J Am Soc Nephrol

Publication Date

04/2013

Volume

24

Pages

759 - 770

Keywords

Adolescent, Adult, Aged, Animals, Cell Survival, Cystathionine beta-Synthase, Cystathionine gamma-Lyase, DNA Damage, Female, HEK293 Cells, Humans, Hydrogen Sulfide, Kidney, Kidney Transplantation, Male, Mice, Mice, Inbred C57BL, Middle Aged, Oxidative Stress, Renin, Reperfusion Injury, Superoxides