Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD(+) and subsequently, ATP, leading to cellular dysfunction and, ultimately, cell death. The key enzyme involved in polymer turnover is PARG, which possesses mainly exoglycosidase activity but can remove olig(ADP-ribose) fragments via endoglycosidic cleavage. Thus, the aim of this study was to investigate whether the absence of PARG(110) reduced the renal dysfunction, injury, and inflammation caused by I/R of the mouse kidney. Here, the renal dysfunction and injury caused by I/R (bilateral renal artery occlusion [30 min] followed by reperfusion [24 h]) in mice lacking PARG(110), the major nuclear isoform of PARG, was investigated. The following markers of renal dysfunction and injury were measured: Plasma urea, creatinine, aspartate aminotransferase, and histology. The following markers of inflammation were also measured: Myeloperoxidase activity, malondialdehyde levels, and plasma nitrite/nitrate. The degree of renal injury and dysfunction caused by I/R was significantly reduced in PARG(110)-deficient mice when compared with their wild-type littermates, and there were no differences in any of the biochemical parameters measured between sham-operated PARG(110)(-/-) mice and sham-operated wild-type littermates. Thus, it is proposed that endogenous PARG(110) plays a pivotal role in the pathophysiology of I/R injury of the kidney.
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PMID:Mice lacking the 110-kD isoform of poly(ADP-ribose) glycohydrolase are protected against renal ischemia/reperfusion injury. 1567 8

Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion injury of various organs. Sulforaphane, which is a naturally occurring isothiocyanate that is present in cruciferous vegetables such as broccoli, is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. Phase 2 enzymes such as heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutathione reductase, and glutathione peroxidase participate in adaptive and protective responses to oxidative stress and various inflammatory stimuli. Therefore, we evaluated the preactivation of Nrf2 by sulforaphane to determine if it could inhibit ischemia-reperfusion-induced kidney damage. Treatment of HK2 renal tubular epithelial cells with sulforaphane effectively protected cells against cytotoxicity induced by hypoxia-reoxygenation, and sulforaphane dramatically induced phase 2 enzymes by decreasing the Keap1 protein levels and increasing Nrf2 nuclear translocation. Additionally, a second set of experiments using a renal ischemia-reperfusion model produced results that were essentially the same as those observed when HK2 cells were used; namely, that sulforaphane induced Nrf2-dependent phase 2 enzymes and thereby improved ischemia-reperfusion-induced changes in the lipid hydroperoxides, glutathione, creatinine clearance, kidney weight, and histologic abnormalities. Collectively, these results suggest that sulforaphane can be used as an effective adjunct for the prevention of renal oxidative insults during ischemia-reperfusion injury.
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PMID:Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme. 1840 46