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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/F27    most recent 00096.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Xu, Z. Articles by O, K. PubMed PubMed Citation Articles by Xu, Z. Articles by O, K.

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

¹Department of Animal Science and ²Department of Physiology, University of Manitoba, and ³St. Boniface Hospital Research Centre, Winnipeg, Manitoba; and ⁴Agriculture and Agri-Food Canada, Ottawa, Ontario, Canada

Submitted 18 February 2009 ; accepted in final form 5 May 2009

Cystathionine-β-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 (H₂S), 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 H₂S production in the kidney and to determine whether changes in the endogenous H₂S 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 H₂S production was decreased, leading to a significant reduction in the renal H₂S level. The activity of cystathionine--lyase, another enzyme responsible for endogenous H₂S 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 H₂S levels but also alleviated ischemia-reperfusion-induced lipid peroxidation and reduced cell damage in the kidney tissue. Furthermore, administration of an exogenous H₂S donor, NaHS (100 µg/kg), improved renal function. Taken together, these results suggest that maintenance of tissue H₂S level may offer a renal protective effect against ischemia-reperfusion injury.

homocysteine; oxidative stress; renal function; cystathionine--lyase