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 effects of renal ischemia on the intracellular distribution of the low-molecular weight heat shock protein (HSP)25 were examined using immunofluorescence microscopy. In all kidney zones, ischemia decreased HSP25 in the supernatant of the tissue homogenates and increased it in the pellet fraction (containing mainly nuclei and cytoskeletal components). This was associated with disappearance of HSP25 staining from the brush border of proximal convoluted tubule (PCT) cells. Because no nuclear staining of cortical tubule cells was apparent either in control or ischemic kidneys, ischemia seems to cause a closer association of HSP25 with cytoskeletal components. HSP25 probably participates in the postischemic restructuring of the cytoskeleton of PCT cells.
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PMID:Effect of ischemia on localization of heat shock protein 25 in kidney. 973 81

We showed previously that activation of A(1) adenosine receptors (AR) protects against renal ischemia-reperfusion (IR) injury in rats and mice. In the heart, transient A(1)AR activation produces biphasic protective effects: acute protection wanes after several hours but protective effects return 24-72 h later (second window of protection). In this study, we determined whether A(1)AR activation produces delayed renal protection and elucidated the mechanisms of acute and delayed renal protection. A(1)AR wild-type mice were subjected to 30-min renal ischemia and 24 h of reperfusion to produce acute renal failure. Pretreatment with a selective A(1)AR agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA; 0.1 mg/kg bolus ip) either 15 min or 24 h before renal ischemia protected against renal IR injury and reduced renal corticomedullary necrosis, apoptosis, and inflammation. Transient A(1)AR activation led to phosphorylation of extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK), Akt, and heat shock protein 27 (HSP27). Moreover, induction of HSP27 and Akt occurred with CCPA treatment. Inhibition of PKC with chelerythrine prevented acute but not delayed renal protection with A(1)AR activation. Moreover, deletion of PI3Kgamma or inhibition of Akt, but not inhibition of ERK, prevented delayed and acute renal protection with A(1)AR activation. Inhibition of G(i/o) with pertussis toxin obliterated both acute and delayed A(1)AR-mediated renal protection. In contrast to renal protection with delayed ischemic preconditioning, nitric oxide synthase activity was not induced with delayed A(1)AR-mediated renal protection. Therefore, transient activation of renal A(1)AR led to acute as well as delayed protective effects against renal IR injury via distinct signaling pathways.
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PMID:Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors. 1792 14

Renal injury is known to trigger upregulation of many intracellular signal proteins, but those most sensitive in responding to renal injury remain debatable. We used gene microarray analysis to compare gene expression in rat kidneys subjected to early ischemia-reperfusion injury (30 min of renal ischemia and 3 hr of reperfusion) with non-ischemic kidneys as controls. Among 31,100 genes analyzed, microarray analysis revealed 21 genes with >3-fold increase in expression in ischemic kidneys compared to control non-ischemic kidneys. These upregulated genes included heat shock protein 70 (43-fold), heat shock protein 27 (12-fold), heme oxygenase-1 (10-fold), kidney injury molecule-1 (8-fold), and several subtypes of S100 calcium-binding proteins (3.1- to 7.5-fold). Following a prolonged reperfusion period (48 hr) after 30 min of ischemia, acute tubular necrosis was obvious in the S3 segment of proximal tubules of ischemic kidneys. Injured proximal tubules showed upregulated expression of heat shock protein 70 by immunohistochemistry and by Western blotting. These data suggest that heat shock proteins (eg, heat shock protein 70, heat shock protein 27, and heme oxygenase-1) are crucial for renal cell response to ischemic injury and that heat shock protein 70 is a highly sensitive intracellular marker of ischemia-reperfusion injury.
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PMID:Heat shock protein expression is highly sensitive to ischemia-reperfusion injury in rat kidneys. 1831 83

We have previously shown that exogenous and endogenous A(1) adenosine receptor (A(1)AR) activation protected against renal ischemia-reperfusion (IR) injury in mice by induction and phosphorylation of heat shock protein 27 (HSP27). With global overexpression of HSP27 in mice, however, there was a paradoxical increase in systemic inflammation with increased renal injury after an ischemic insult due to increased NK1.1 cytotoxicity. In this study, we hypothesized that selective renal expression of HSP27 in mice would improve renal function and reduce injury after IR. Mice were subjected to renal IR injury 2 days after intrarenal injection of saline or a lentiviral construct encoding enhanced green fluorescent protein (EGFP) or human HSP27 coexpressing EGFP (EGFP-huHSP27). Mice with kidney-specific reconstitution of huHSP27 had significantly lower plasma creatinine, renal necrosis, apoptosis, and inflammation as demonstrated by decreased proinflammatory cytokine mRNA induction and neutrophil infiltration. In addition, there was better preservation of the proximal tubule epithelial filamentous (F)-actin cytoskeleton in the huHSP27-reconstituted groups than in the control groups. Furthermore, huHSP27 overexpression led to increased colocalization with F-actin in renal proximal tubules. Taken together, these findings have important clinical implications, as they imply that kidney-specific expression of HSP27 through lentiviral delivery is a viable therapeutic option in attenuating the effects of renal IR.
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PMID:Selective renal overexpression of human heat shock protein 27 reduces renal ischemia-reperfusion injury in mice. 2048 96