Ischemia-reperfusion reduces cystathionine-beta-synthase-mediated hydrogen sulfide generation in the kidney.

Abstract

Cystathionine-beta-synthase (CBS) catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of homocysteine (Hcy) in the kidney. Our recent study demonstrates that ischemia-reperfusion reduces the activity of CBS leading to Hcy accumulation in the kidney, which in turn contributes to renal injury. CBS is also capable of catalyzing the reaction of cysteine with Hcy to produce hydrogen sulfide (H(2)S), a gaseous molecule that plays an important role in many physiological and pathological processes. The aim of the present study was to examine the effect of ischemia-reperfusion on CBS-mediated H(2)S production in the kidney and to determine whether changes in the endogenous H(2)S generation had any impact on renal ischemia-reperfusion injury. The left kidney of Sprague-Dawley rat was subjected to 45-min ischemia followed by 6-h reperfusion. The ischemia-reperfusion caused lipid peroxidation and cell death in the kidney. The CBS-mediated H(2)S production was decreased, leading to a significant reduction in the renal H(2)S level. The activity of cystathionine-gamma-lyase, another enzyme responsible for endogenous H(2)S generation, was not significantly altered in the kidney upon ischemia-reperfusion. Partial restoration of CBS activity by intraperitoneal injection of the nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide not only increased renal H(2)S levels but also alleviated ischemia-reperfusion-induced lipid peroxidation and reduced cell damage in the kidney tissue. Furthermore, administration of an exogenous H(2)S donor, NaHS (100 microg/kg), improved renal function. Taken together, these results suggest that maintenance of tissue H(2)S level may offer a renal protective effect against ischemia-reperfusion injury.

• Authors: Zhibin Xu, Gamika Prathapasinghe, Nan Wu, Sun-Young Hwang, Yaw L Siow, Karmin O
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 297 Issue 1 Pg. F27-35 (Jul 2009) ISSN: 1522-1466 [Electronic] United States
• PMID: 19439522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic N-Oxides
• Free Radical Scavengers
• Imidazoles
• Homocysteine
• 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
• Nitric Oxide
• Cystathionine beta-Synthase
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Apoptosis (drug effects)
• Cyclic N-Oxides (pharmacology)
• Cystathionine beta-Synthase (metabolism)
• Cystathionine gamma-Lyase (metabolism)
• Disease Models, Animal
• Free Radical Scavengers (pharmacology)
• Homeostasis
• Homocysteine (metabolism)
• Hydrogen Sulfide (metabolism, pharmacology)
• Imidazoles (pharmacology)
• Kidney (drug effects, metabolism, pathology)
• Male
• Nitric Oxide (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)