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)

Both glutathione and glycine provide some protection against ischemic renal injury in a variety of experimental models. However, results have been inconsistent and there may also be model heterogeneity. The effects of glutathione, glycine, and alanine in a cell culture model of renal anoxia/reoxygenation injury were tested. When primary cultures of rat proximal tubule epithelial cells were subjected to 60 min of anoxia and 30 min of reoxygenation, glutathione (2 mM) essentially eliminated lethal cell injury as determined by lactate dehydrogenase release. Glycine or alanine, on the other hand, provided only partial protection. Glutamate did not protect, although cysteine did. The glutathione synthesis inhibitor buthionine sulfoximine blocked the protective effect of exogenous glutathione, and the glutathione transport inhibitor probenecid partially blocked glutathione protection. A combination of glycine, glutamate, plus cysteine also protected against anoxia/reoxygenation injury. The studies suggest that both glutathione degradation with intracellular resynthesis and transport of intact glutathione into the cell are involved in the protection afforded by exogenous glutathione. These results are different from those obtained in other experimental models of renal ischemia, such as freshly isolated proximal tubules, because the protective effects of glutathione were not derived solely from glycine generation. These studies also suggest the need for caution in extrapolating results from one model of renal anoxic injury to another.
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PMID:Protective effects of glutathione, glycine, or alanine in an in vitro model of renal anoxia. 162 58

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing of prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time.
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PMID:Human renin biosynthesis and secretion in normal and ischemic kidneys. 331 96

The effects of hypothermic ischemia utilizing Euro-Collins flush on renal tissue long-chain activated fatty acid content was studied in dogs. Also, the ability of the simple amino acid glycine to complex these acyl thioesters was also investigated. Renal inner cortex was found to contain (in increasing amounts) myristoyl-, palmitoleoyl-, palmitoyl-, arachidonyl-, and oleoyl-coenzyme A throughout the 3 days of cold ischemia. Although the amounts of individual long-chain acyl-CoA compounds varied considerably, the concentrations were not found to differ significantly with increasing ischemia times. The presence of 5 mM of glycine in the flush also did not influence the amount or species of long-chain acyl-CoA esters in renal tissue during cold ischemia. Ischemic renal tissue content of most long-chain acyl-CoA compounds was reduced by about 50% when the tissue underwent in vitro reperfusion with 37 degrees C O2-saturated media. Glycine included in the flush storage solution did not alter acyl-CoA levels in tissue undergoing hypothermic ischemia and short-term in vitro reperfusion with O2-saturated buffer. In conclusion, long-chain acyl-CoA thioesters are present during hypothermic renal ischemia and the levels of most of these species are reduced during in vitro reperfusion after ischemia. The quality and production mass of these metabolites appears to be unaltered by progressive hypothermic ischemia times. Finally, the protective effects of glycine in this model of renal organ preservation injury are not associated with reductions of renal tissue long-chain activated fatty acids.
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PMID:Long-chain acyl-coenzyme A thioesters and renal hypothermic ischemic injury: effects of glycine flush. 844 Jan 27

Reorientation of the alpha 3 subunit of integrins from predominantly basal to the apical cell surface of cultured renal tubular epithelial cells subjected to oxidant stress has previously been demonstrated. The present study was designed to assess functional competence of ectopically expressed apical integrins. Cell-cell adhesion assay revealed enhanced cytoatractant properties of stressed cells. Stressed epithelial cells exhibited specific recognition and binding of laminin-coated latex beads. These processes were inhibited with the peptide Gly-Arg-Gly-Asp-Asn-Pro (GRGDNP) suggesting a role of RGD-recognizing integrins in augmented adhesion to stressed cells. Given that such enhanced adhesion in in vivo acute renal failure may govern tubular obstruction by desquamated epithelium, a physiological marker of patency of tubular lumen, proximal tubular pressure, was monitored in rats subjected to 60 min of renal ischemia followed by reperfusion. Proximal tubular pressure increased 2-fold after 2 hr of reperfusion in animals that had undergone 60 min of ischemia. Infusion of GRGDNP into the renal artery during reperfusion period virtually abolished an increase in proximal tubular pressure observed in ischemic acute renal failure. These in vitro and in vivo findings are consistent with the hypothesis that RGD-recognizing integrins play an important role in the pathogenesis of tubular obstruction in ischemic acute renal failure.
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PMID:Pathogenetic role of Arg-Gly-Asp-recognizing integrins in acute renal failure. off. 851 18

Renal ischemia/reperfusion is a common cause of acute renal failure. Glycine is an effective anti-inflammatory, cytoprotective agent and is reported to have a beneficial effect against ischemia/reperfusion injury in various organs. Previous research notes that free radicals and inflammatory leukocytes both play important roles in the pathogenesis of renal ischemia/reperfusion injury. To develop new therapeutic agents against renal ischemia/reperfusion injury, we sought to link an antioxidant moiety (nitronyl nitroxide) to glycine in the hope that the resulting glycine-nitronyl nitroxide conjugate (GNN) would provide a synergetic protection against renal ischemia/reperfusion injury. In this manuscript, we report the synthesis and biological evaluation of the GNN conjugate. The biological activity of the GNN conjugate was evaluated in an in vivo rat model of renal ischemia/reperfusion induced injury and oxidative change. Since the GNN conjugate markedly reduced elevated levels of tissue lipid peroxidation and attenuated renal dysfunction in rats subjected to renal ischemia/reperfusion, it might be possible to develop the GNN conjugate into a potential therapeutic agent against renal ischemia/reperfusion injury.
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PMID:Renal ischemia/reperfusion injury in rats is attenuated by a synthetic glycine derivative. 1955 83

Endothelial progenitor cells (EPCs) protect kidneys from acute ischemic damage. The aim of this study was to identify "treatment parameters" that optimize an EPC-based therapy of acute ischemic renal failure. Male C57BL/6N mice underwent unilateral nephrectomy with simultaneous contralateral renal artery clamping for 30, 35, and 40 min. Tagged murine EPCs were systemically injected at the time of reperfusion. In some experiments, EPCs were pretreated with the Epac (exchange protein directly activated by cAMP-1) activator 8-pCPT-2'-O-Me-cAMP (Epac-1 Ac) and the integrin binding antagonist cyclic Arg-Gly-Asp peptide (cRGD). Injections of 10(6) EPCs after 30 and 35 min of renal ischemia protected animals from acute renal failure. The same effect occurred with 0.5 x 10(6) EPCs after a 35-min period of ischemia. If ischemia lasted for 40 min, 0.5 x 10(6) cells mice did not prevent acute renal failure. To analyze whether EPC integrin receptor activation would modify the cells' renoprotective activity, EPCs were pretreated with Epac-1 Ac. Such animals did not develop acute renal failure, even if ischemia lasted for 40 min. This effect was negated if the cells were pretreated with both Epac-1 Ac and cRGD. In kidneys from those animals medullopapillary EPCs were significantly accumulated. In vitro Epac-1 Ac preactivation of EPCs did not increase the overall expression intensity but induced a redistribution of beta(1)-integrins toward the cell membranes. We conclude that EPC pretreatment with the integrin receptor activator 8-pCPT-2'-O-Me-cAMP augments the anti-ischemic potential of the cells.
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PMID:Epac-1 activator 8-O-cAMP augments renoprotective effects of syngeneic [corrected] murine EPCs in acute ischemic kidney injury. 1990 49

The present study was designed to investigate the role of glycine in ischemia reperfusion-induced acute kidney injury (AKI) in rats. The AKI was induced in rats by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium, fractional excretion of sodium, and microproteinuria. The oxidative stress in renal tissues was assessed by quantification of myeloperoxidase activity, thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. Glycine (100, 200, and 400 mg/kg, i.p.) was administered to rats 30 min before subjecting to AKI. The glycinergic receptor blocker, strychnine (0.75 mg/kg i.p.), and glycine-binding site blocker at N-methyl-D-aspartate (NMDA) receptor, kynurenic acid (300 and 600 mg/kg i.p.), were used in the present study. The ischemia reperfusion induced AKI as witnessed by significant change in plasma, urinary, and tissue parameters employed in the present study. Glycine treatment increased ischemia reperfusion-induced AKI. The treatment with strychnine did not show any protection, whereas kynurenic acid ameliorated renal ischemia reperfusion-induced AKI. The results obtained in present study suggest that glycine increases ischemia reperfusion-induced renal damage through NMDA receptor agonism rather than strychnine-sensitive glycinergic receptors. Hence, it is concluded that glycine aggravates ischemia reperfusion-induced AKI. In addition, the activation of strychnine-insensitive glycine-binding site of NMDA receptors is responsible for its renal-damaging effect rather than strychnine-sensitive glycinergic receptors.
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PMID:Glycine aggravates ischemia reperfusion-induced acute kidney injury through N-Methyl-D-Aspartate receptor activation in rats. 2474 Jul 57