The majority of small G-proteins undergo posttranslational modifications (e.g., isoprenylation) at their C-terminal cysteine residues. Such modifications increase their hydrophobicity, culminating in translocation of the modified proteins to their relevant membranous sites for interaction with their respective effectors. Previously, we reported glucose-dependent activation and membrane association of

McDonald P, Veluthakal R, Kaur H, Kowluru A. Biologically active lipids promote trafficking and membrane association of Rac1 in insulin-secreting INS 832/13 cells.

Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.