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Cystathionine γ-lyase protects against renal ischemia/reperfusion by modulating oxidative stress.

Abstract
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.
AuthorsEelke M Bos, Rui Wang, Pauline M Snijder, Miriam Boersema, Jeffrey Damman, Ming Fu, Jill Moser, Jan-Luuk Hillebrands, Rutger J Ploeg, Guangdong Yang, Henri G D Leuvenink, Harry van Goor
JournalJournal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 24 Issue 5 Pg. 759-70 (Apr 2013) ISSN: 1533-3450 [Electronic] United States
PMID23449534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Superoxides
  • Renin
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide
Topics
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Survival
  • Cystathionine beta-Synthase (physiology)
  • Cystathionine gamma-Lyase (analysis, genetics, physiology)
  • DNA Damage
  • Female
  • HEK293 Cells
  • Humans
  • Hydrogen Sulfide (metabolism)
  • Kidney (blood supply, enzymology)
  • Kidney Transplantation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Oxidative Stress
  • Renin (analysis)
  • Reperfusion Injury (prevention & control)
  • Superoxides (metabolism)

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