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)

In human and murine models of sickle cell disease (SCD), heme oxygenase-1 (HO-1) is induced in the kidney, an organ commonly involved in SCD. The present study assessed the role of HO-1 by using a competitive inhibitor of HO activity, tin protoporphyrin (SnPP), in protocols affording a composite, clinically relevant analysis of the kidney in SCD under unstressed and stressed conditions. Whereas short-term administration of SnPP exerted comparable renal hemodynamic effects in wild-type and sickle mice, chronic administration of SnPP exerted divergent effects: SnPP provoked tubulointerstitial inflammation and up-regulation of injury-related genes in wild-type mice, whereas in sickle mice SnPP reduced expression of injury-related genes and vascular congestion without provoking tubulointerstitial inflammation. SnPP also protected against the heightened sensitivity to renal ischemia observed in sickle mice, preventing ischemia-induced worsening of renal injury in sickle mice above that observed in wild-type mice. Effective and comparable inhibition of HO activity by SnPP in wild-type and sickle mice was confirmed. These findings suggest that induction of HO-1, at least as assessed by this approach, may contribute to renal injury in this murine model of SCD and uncover an experimental maneuver that protects the kidney in murine SCD.
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PMID:Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease. 1681 58

Statins induce heme oxygenase-1 (HO-1) in several cell types, such as vascular smooth muscle cells, endothelial cells, and macrophages. The present study assessed the role of statin-induced HO-1 up-regulation on circulating monocytes/macrophages and their contribution in preventing renal ischemia-reperfusion (IR) injury in a rat model. Cerivastatin was administered via gavage (0.5 mg/kg) for 3 days before IR injury; controls received vehicle. Statin pretreatment reduced renal damage and attenuated renal dysfunction (P < 0.05) after IR injury. The protective statin pretreatment effect was completely abolished by cotreatment with tin protoporphyrin IX (Sn-PP), a competitive HO inhibitor. IR increased HO-1 expression at the transcript and protein level in renal tissue. This effect was significantly more evident (P < 0.05) in the statin-pretreated animals 24 hours after IR injury. We identified infiltrating macrophages as the major source of tissue HO-1 production. Moreover, in ancillary cell culture (monocyte cell line) and in in vivo experiments (isolation of circulating monocytes), we confirmed that statins regulate HO-1 expression in these cells. We conclude that statin treatment up-regulates HO-1 in circulating monocytes/macrophages in vivo and in vitro. We hypothesize that local delivery of HO-1 from infiltrating macrophages exerts anti-inflammatory effects after IR injury and thereby may reduce tissue destruction.
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PMID:Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages. 1739 59

Osteopontin plays a pivotal role in the progression of interstitial fibrosis in renal ischemia. In the present study, rat renal tubular NRK52E cells treated with hypoxia mimetic cobalt chloride (CoCl(2)) increased osteopontin production, and are associated with increased phosphorylation of Akt/PKB (protein kinase B) and p38 mitogen-activated protein kinase (p38MAPK). Furthermore, pretreatment of cells with l-N-acetylcysteine (an antioxidant) inhibited CoCl(2)-stimulated osteopontin protein expression and p38MAPK phosphorylation, but not Akt/PKB phosphorylation. Pretreatment of cells with anti-inflammatory agents celecoxib, tanshinone IIA, and dipyridamole inhibited CoCl(2)-induced osteopontin production paralleled by heme oxygenase-1 (HO-1) induction. Pretreatment of cells with tin protoporphyrin (a HO-1 inhibitor) or hemoglobin (a carbon monoxide scavenging agent) reversed dipyridamole inhibition of osteopontin expression. Moreover, transfection of HO-1 small interfering RNA (siRNA) reduced dipyridamole-stimulated mitogen-activated protein kinase phosphatase-1 (MKP-1) phosphorylation. Conversely, MKP-1 knockdown reversed dipyridamole inhibition of osteopontin expression. Taken together, these data suggest that dipyridamole may inhibit CoCl(2)-induced osteopontin expression through HO-1 induction. Increased HO-1 may catalyze the conversion of heme into carbon monoxide, in turn carbon monoxide activates MKP-1. MKP-1 activation inhibits the p38MAPK signaling pathway that mediates CoCl(2)-induced osteopontin production.
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PMID:Dipyridamole inhibits cobalt chloride-induced osteopontin expression in NRK52E cells. 1935 21