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)

To understand the mechanisms underlying ischemia-reperfusion-induced renal proximal tubule damage, we analyzed the expression of the Na+-dependent phosphate (Na+/Pi) cotransporter NaPi-2 in brush border membranes (BBM) isolated from rats which had been subjected to 30 min renal ischemia and 60 min reperfusion. Na+/Pi cotransport activities of the BBM vesicles were also determined. Ischemia caused a significant decrease (about 40%, P < 0.05) in all forms of NaPi-2 in the BBM, despite a significant increase (31+/-3%, P < 0.05) in the Na+/Pi cotransport activity. After reperfusion, both NaPi-2 expression and Na+/Pi cotransport activity returned to control levels. In contrast with Na+/Pi cotransport, ischemia significantly decreased Na+-dependent glucose cotransport but did not affect Na+-dependent proline cotransport. Reperfusion caused further decreases in both Na+/glucose (by 60%) and Na+/proline (by 33%) cotransport. Levels of NaPi-2 were more reduced in the BBM than in cortex homogenates, suggesting a relocalization of NaPi-2 as a result of ischemia. After reperfusion, NaPi-2 levels returned to control values in both BBM and homogenates. These data indicate that the NaPi-2 protein and BBM Na+/Pi cotransport activity respond uniquely to reversible renal ischemia and reperfusion, and thus may play an important role in maintaining and restoring the structure and function of the proximal tubule.
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PMID:Effect of ischemia-reperfusion on the renal brush-border membrane sodium-dependent phosphate cotransporter NaPi-2. 1129 96

Previous studies have demonstrated that levels of tumor necrosis factor-alpha (TNF-alpha) or its mRNA expression are increased in acute renal failure of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-alpha production, provides a protective effect against ischemic acute renal failure in rabbits. Renal ischemia was induced by clamping bilateral renal arteries for 60 min. Animals were pretreated with PTX (30 mg/kg, i.v.) 10 min before release of clamp. At 24 h of reperfusion of blood after ischemia, changes in renal function, renal blood flow, and the expression of TNF-alpha mRNA were evaluated. Ischemia/reperfusion caused a marked reduction in GFR, which was accompanied by an increase of serum creatinine levels. Such changes were significantly attenuated by PTX pretreatment. PTX ameliorated the impairment of renal tubular function, but it had no effect on the reduction of renal blood flow induced by ischemia/reperfusion. The protective effect of PTX on functional changes was supported by morphological studies. The impairment of glucose and phosphate reabsorption in postischemic kidneys was associated with a depression in the expression of Na+-glucose and Na+-Pi transporters. The expression of TNF-alpha mRNA was increased after reperfusion, which was inhibited by PTX pretreatment. The PTX pretreatment in vitro prevented the release of lactate dehydrogenase induced by an oxidant t-butylhydroperoxide in rabbit renal cortical slices, but it did not produce any effect on the oxidant-induced lipid peroxidation, suggesting that PTX protection is not resulted from its antioxidant action. These results suggest that PTX may exert a protective effect against ischemic acute renal failure by inhibiting the production of TNF-alpha in rabbits.
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PMID:Effect of pentoxifylline on ischemic acute renal failure in rabbits. 1177 15

Biotin-cysteine was used to study protein S-thiolation in isolated rat kidneys subjected to ischemia and reperfusion. After 40 min of ischemia, total protein S-thiolation increased significantly (P < 0.05), by 311%, and remained significantly elevated (P < 0.05), 221% above control, after 5 min of postischemic reperfusion. Treatment of protein samples with 2-mercaptoethanol abolished the S-thiolation signals detected, consistent with the dependence of the signal on the presence of a disulfide bond. With the use of gel filtration chromatography followed by affinity purification with streptavidin-agarose, S-thiolated proteins were purified from CHAPS-soluble kidney homogenate. The proteins were then separated by SDS-PAGE and stained with Coomassie blue. With a combination of matrix-assisted laser desorption ionization time of flight mass spectrometry and LC/MS/MS analysis of protein bands digested with trypsin, a number of S-thiolation substrates were identified. These included the LDL receptor-related protein 2, ATP synthase alpha chain, heat shock protein 90 beta, hydroxyacid oxidase 3, serum albumin precursor, triose phosphate isomerase, and lamin. These represent proteins that may be functionally regulated by S-thiolation and thus could undergo a change in activity or function after renal ischemia and reperfusion.
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PMID:Reversible cysteine-targeted oxidation of proteins during renal oxidative stress. 1287 48

Therapeutic effects of acidic fibroblast growth factor on postischemic renal injury were evaluated in a rat model of bilateral renal ischemia (60 minutes) and reperfusion (7 days). Twenty-four rats were randomly divided into two groups (12 rats each). After 60 minutes of ischemia and at the onset of reperfusion, rats in the acidic fibroblast growth factor-treated group received 2.6 microg of acidic fibroblast growth factor/rat in 50 microl of phosphate-buffered saline solution containing 0.1% heparin (w/v) through the jugular vein, whereas the rats in the phosphate-buffered saline solution-treated group received the same vehicle without acidic fibroblast growth factor. Compared with the phosphate-buffered saline solution-treated group, rats in the acidic fibroblast growth factor-treated group had significantly lower blood urea nitrogen (83.13 +/- 26.07 versus 176.36 +/- 62.36, p < 0.05) and serum creatinine (0.73 +/- 0.14 versus 1.14 +/- 0.36, p < 0.05) levels 1 day after occlusion. Histopathologic scores showed much less renal damage on day 1 in the acidic fibroblast growth factor-treated rats compared with the phosphate-buffered saline solution controls. We conclude that intravenous administration of acidic fibroblast growth factor offers significant protection against postischemic renal injury and these protective effects may come from its nonmitogenic effects such as the regulation of vessel tone and calcium concentration in the body.
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PMID:Acidic fibroblast growth factor reduces renal morphologic and functional indicators of injury caused by ischemia and reperfusion. 1717 27

T cells are thought to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI); however, earlier studies have not found significant T-cell numbers in the kidney following injury. In this study we test the hypothesis that T cells transiently infiltrate the kidney following reperfusion and leave behind T-cell-derived cytokines such as interferons and interleukins, thus triggering an inflammatory reaction. An early rise of infiltrating T cells was coupled with a decrease in both circulating lymphocytes and CD4+ cells of periarterial lymphocyte aggregates. The renal expression of several chemokines was rapidly and markedly increased by ischemia-reperfusion (IR). Sphingosine-1-phosphate type 1 receptor agonists have been shown to protect kidneys from injury. One of these agonists given before IR significantly reduced histologically assessed renal injury, circulating lymphocyte numbers, and renal T-cell infiltration. This pretreatment did not, however, affect the increase in T-cell chemokines but caused an increase in CD4+ cells in the renal lymphatic system. We conclude that T-cell infiltration is an early event after IRI and is mediated by several chemokines. Sphingosine-1-phosphate receptor agonists reduce renal injury and T-cell infiltration in spite of chemokine generation by inhibiting T-cell mobilization from both renal and extra-renal lymphoid tissue.
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PMID:A sphingosine-1-phosphate type 1 receptor agonist inhibits the early T-cell transient following renal ischemia-reperfusion injury. 1755 48

The inhalational anesthetic isoflurane has been shown to protect against renal ischemia-reperfusion (IR) injury. Previous studies demonstrated that isoflurane modulates sphingolipid metabolism in renal proximal tubule cells. We sought to determine whether isoflurane stimulates sphingosine kinase (SK) activity and synthesis of sphingosine-1-phosphate (S1P) in renal proximal tubule cells to mediate renal protection via the S1P signaling pathway. Isoflurane anesthesia reduced the degree of renal failure and necrosis in a murine model of renal IR injury. This protection with isoflurane was reversed by SK inhibitors (DMS and SKI-II) as well as an S1P(1) receptor antagonist (VPC23019). In addition, mice deficient in SK1 enzyme were not protected from IR injury with isoflurane. SK activity as well as SK1 mRNA expression increased in both cultured human proximal tubule cells (HK-2) and mouse kidneys after exposure to isoflurane. Finally, isoflurane increased the generation of S1P in HK-2 cells. Taken together, our findings indicate that isoflurane activates SK in renal tubule cells and initiates S1P-->S1P(1) receptor signaling to mediate the renal protective effects. Our findings may help to unravel the cellular signaling pathways of volatile anesthetic-mediated renal protection and lead to new therapeutic applications of inhalational anesthetics during the perioperative period.
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PMID:Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways. 1789 40

The cellular pathophysiology of renal ischemia-reperfusion injury was investigated in primary cell cultures from rabbit medullary thick ascending limb (MTAL). Metabolic inhibition (MI) was achieved with cyanide and 2-deoxyglucose. Sixty minutes of MI caused a profound but reversible decrease in intracellular concentration of ATP ([ATP]i). Intracellular pH (pHi) first decreased after initiation of MI, followed by a transient alkalinization. When [ATP]i reached its lowest value (<1% of control), the cells slowly acidified to reach a stable pHi of 6.92 after 50 min of MI. In the presence of EIPA (10 micromol/L), the pattern of changes in pHi was unchanged and acidification was not increased, indicating that the Na+/H+ exchangers were inactive during ATP depletion. When inorganic phosphate (P(i)) or Na+ was omitted from the apical solutions during MI, the transient alkalinization was no longer observed and the cytosol slowly acidified. Experiments on Na+-dependent alkalinizations revealed the presence of a Na-P(i) cotransporter in the apical cell membrane. With indirect immunofluorescence, the Na-P(i) cotransporter expressed in these primary cell cultures could be identified as Na-P(i) type I. Although the exact physiological role of Na-P(i) type I still is unresolved, these experiments demonstrate that apical Na-P(i) type I activity is increased at the onset of ATP depletion in MTAL cells.
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PMID:Na-P(i) cotransporter type I activity causes a transient intracellular alkalinization during ATP depletion in rabbit medullary thick ascending limb cells. 1841 45

Agonists of the sphingosine-1-phosphate receptor (S1PR) attenuate kidney ischemia-reperfusion injury (IRI). Previous studies suggested that S1P1R-induced lymphopenia mediates this protective effect, but lymphocyte-independent mechanisms could also contribute. Here, we investigated the effects of S1PR agonists on kidney IRI in mice that lack T and B lymphocytes (Rag-1 knockout mice). Administration of the nonselective S1PR agonist FTY720 or the selective S1P1R agonist SEW2871 reduced injury in both Rag-1 knockout and wild-type mice. In vitro, SEW2871 significantly attenuated LPS- or hypoxia/reoxygenation-induced apoptosis in cultured mouse proximal tubule epithelial cells, supporting a direct protective effect of S1P1R agonists via mitogen-activated protein kinase and/or Akt pathways. S1P1Rs in the proximal tubule mediated IRI in vivo as well: Mice deficient in proximal tubule S1P1Rs experienced a greater decline in renal function after IRI than control mice and their kidneys were no longer protected by SEW2871 administration. In summary, S1PRs in the proximal tubule are necessary for stress-induced cell survival, and S1P1R agonists are renoprotective via direct effects on the tubule cells. Selective agonists of S1P1Rs may hold therapeutic potential for the prevention and treatment of acute kidney injury.
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PMID:Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury. 2468 18

Extracellular superoxide dismutase (SOD3) is highly expressed in renal tissues and a critical regulator of vascular function. We hypothesized that deletion of SOD3 would attenuate recovery of renal blood flow (RBF) and increase oxidative stress and injury following renal ischemia/reperfusion (I/R). To test this, we evaluated SOD expression and activity, basal superoxide production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in kidneys from male and female wild-type (WT) and SOD3-knockout mice. RBF, measured using an ultrasonic flow probe, and histological indices of oxidative stress and injury were assessed after 1 h of ischemia. Following ischemia, RBF was attenuated in kidneys from male, but not female, knockout mice compared with their WT counterparts. Total SOD activity was significantly reduced in male knockout compared with WT male mice but was similar in female mice of both genotypes, suggesting upregulated SOD1 activity. Basal superoxide production and NADPH oxidase activity were unrelated to the differences in RBF. After 24 h, kidneys from both genders of knockout mice were found to have more oxidative stress (3-nitrotyrosine immunohistochemistry) and renal cast formation than those from WT mice. Thus, our study found a key role for SOD3 in regulating renal I/R injury.
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PMID:Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury. 2050 56

Phosphocreatine (PCr) is an endogenous compound containing high-energy phosphate bonds. It has been confirmed that PCr is effective in preventing and treating cardiac and renal ischemia-reperfusion injury. In this study, rat cerebral ischemia-reperfusion injury models were constructed. Apoptotic cells in the cortex region were measured by TUNEL method. Malondialdehyde (MDA) content was detected by chromatometry, and calmodulin (CaM) activity was detected by ELISA. Compared with sham-operated group (sham group), TUNEL-positive cells, MDA, and level of CaM activity increased in ischemia-reperfusion group (I/R group) and PCr preconditioning group (PCr group); compared with I/R group, TUNEL-positive cells, MDA content, and level of CaM activity decreased in PCr group. This study indicated that PCr can decrease the morphological damage and the neuron apoptosis of the ischemia-reperfusion injury brain through attenuating abnormalities of calcium balance and production of oxygen free radicals.
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PMID:Phosphocreatine preconditioning attenuates apoptosis in ischemia-reperfusion injury of rat brain. 2131 85


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