Regulation and Immunohistochemical Analysis of Stress Protein Heme Oxygenase-1 in Rat Kidney with Myoglobinuric Acute Renal Failure

1997 ◽  
Vol 240 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Shino Ishizuka ◽  
Yoji Nagashima ◽  
Mari Numata ◽  
Tomohiro Yano ◽  
Kiyokazu Hagiwara ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Rat Kidney ◽  
Stress Protein ◽  
Immunohistochemical Analysis ◽  
Heme Oxygenase 1 ◽  
Myoglobinuric Acute Renal Failure

Theophylline protects against glycerol-induced acute renal failure: Regulation of heme oxygenase-1 and glutathione in rat kidney

1997 ◽  
Vol 1 (3) ◽  
pp. 204-211 ◽  
Author(s):  
Shino Ishizuka ◽  
Yoji Nagashima ◽  
Masayoshi Sone ◽  
Kiyokazu Hagiwara ◽  
Saburo Horikawa
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Rat Kidney ◽  
Heme Oxygenase 1

Induction of heme oxygenase-1 in toxic renal injury: mercuric chloride-induced acute renal failure in rat

1998 ◽  
Vol 94 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Saburo Horikawa ◽  
Koji Ito ◽  
Satoru Ikeda ◽  
Toshikazu Shibata ◽  
Shino Ishizuka ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Mercuric Chloride ◽  
Renal Injury ◽  
Heme Oxygenase 1

Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite

2007 ◽  
Vol 293 (6) ◽  
pp. H3542-H3549 ◽  
Author(s):  
Miguel G. Salom ◽  
Susana Nieto Cerón ◽  
Francisca Rodriguez ◽  
Bernardo Lopez ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Medullary Blood Flow ◽  
Ischemic Renal Failure ◽  
Oxide Synthase

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (–SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 ± 129.3 to 2,928.6 ± 502.0 nM and from 3.8 ± 0.7 to 9.0 ± 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and –SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 ± 66.0 and 253.6 ± 55.3 μl·min−1·g kidney wt−1 in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl2 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 ± 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl2 administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 ± 445.6 nM and 6.3 ± 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 ± 45.2 μl·min−1·g kidney wt−1). These beneficial effects of CoCl2 on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.

scholarly journals Exacerbation of Chronic Renovascular Hypertension and Acute Renal Failure in Heme Oxygenase-1–Deficient Mice

2001 ◽  
Vol 88 (10) ◽  
pp. 1088-1094 ◽  
Author(s):  
Philippe Wiesel ◽  
Anand P. Patel ◽  
Irvith M. Carvajal ◽  
Zhi Yuan Wang ◽  
Andrea Pellacani ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renovascular Hypertension ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Deficient Mice

scholarly journals Ischemic and nephrotoxic acute renal failure are distinguished by their broad transcriptomic responses

2006 ◽  
Vol 25 (3) ◽  
pp. 375-386 ◽  
Author(s):  
Peter S. T. Yuen ◽  
Sang-Kyung Jo ◽  
Mikaela K. Holly ◽  
Xuzhen Hu ◽  
Robert A. Star
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Mercuric Chloride ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Protein Detection ◽  
Taqman Assay ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Outer Stripe

Acute renal failure (ARF) has a high morbidity and mortality. In animal ARF models, effective treatments must be administered before or shortly after the insult, limiting their clinical potential. We used microarrays to identify early biomarkers that distinguish ischemic from nephrotoxic ARF or biomarkers that detect both injury types. We compared rat kidney transcriptomes at 2 and 8 h after ischemia/reperfusion and after mercuric chloride. Quality control and statistical analyses were necessary to normalize microarrays from different lots, eliminate outliers, and exclude unaltered genes. Principal component analysis revealed distinct ischemic and nephrotoxic trajectories and clear array groupings. Therefore, we used supervised analysis, t-tests, and fold changes to compile gene lists for each group, exclusive or nonexclusive, alone or in combination. There was little network connectivity, even in the largest group. Some microarray-identified genes were validated by TaqMan assay, ruling out artifacts. Western blotting confirmed that heme oxygenase-1 (HO-1) and activating transcription factor-3 (ATF3) proteins were upregulated; however, unexpectedly, their localization changed within the kidney. HO-1 staining shifted from cortical (early) to outer stripe of the outer medulla (late), primarily in detaching cells, after mercuric chloride but not ischemia/reperfusion. ATF3 staining was similar, but with additional early transient expression in the outer stripe after ischemia/reperfusion. We conclude that microarray-identified genes must be evaluated not only for protein levels but also for anatomical distribution among different zones, nephron segments, or cell types. Although protein detection reagents are limited, microarray data lay a rich foundation to explore biomarkers, therapeutics, and the pathophysiology of ARF.

Role of heme oxygenase-1 in endotoxemic acute renal failure

2005 ◽  
Vol 289 (6) ◽  
pp. F1382-F1385 ◽  
Author(s):  
Brian Poole ◽  
Wei Wang ◽  
Yung-Chang Chen ◽  
Einath Zolty ◽  
Sandor Falk ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Cell Injury ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Renal Protection ◽  
Renal Vasoconstriction

The pathogenesis of septic acute renal failure (ARF) involves systemic vasodilation with compensatory upregulation of vasoconstrictors. This can lead to renal vasoconstriction and ARF. Heme oxygenase (HO) is the rate-limiting step in heme metabolism and produces carbon monoxide (CO) and biliverdin. HO-1 is an inducible form of the enzyme and is expressed in response to cell injury. It was hypothesized in endotoxemia, induction of HO-1 would lead to increased production of the vasodilator CO, lower blood pressure, and decrease renal function. The role of HO-1 was therefore examined in a mouse model of endotoxemia. One group of mice received LPS alone and were compared with mice that received LPS in addition to an inhibitor of HO-1, zinc protoporphyrin (ZnPP). Treatment of mice with LPS resulted in significant increases in the protein expression of HO-1 compared with controls treated with vehicle. Immunohistochemical analysis localized this upregulation to both the proximal and distal tubules as well as the vasculature. Hemodynamic studies were performed during endotoxemia and the mean arterial pressure (MAP) was found to be significantly higher in the HO-1 inhibitor-treated compared with vehicle-treated mice (78 ± 3 vs. 64 ± 2 mmHg, P < 0.01). It was found that the inhibitor group had higher renal blood flows (RBF) also during endotoxemia (1.8 ± 0.2 vs. 0.68 ± 0.1 ml/min, P < 0.01). Furthermore, when renal vascular resistance (RVR) was calculated, there was a significant decrease in RVR in the inhibitor group (43.5 ± 3.4 vs. 95.9 ± 11.3 mmHg·ml−1·min−1, P < 0.01). In concert with the hemodynamic data, glomerular filtration rate (GFR), as measured by inulin clearance, was higher in the HO inhibitor compared with the vehicle controls during endotoxemia (111.5 ± 19.5 vs. 66.0 ± 3.5 μl/min, P < 0.05). In summary, during endotoxemia ARF, inhibiting HO-1 with ZnPP resulted in the protection of renal function. The renal protection was associated with significantly improved systemic hemodynamics, less renal vasoconstriction, and a higher GFR.

scholarly journals Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure

2013 ◽  
Vol 304 (1) ◽  
pp. R10-R22 ◽  
Author(s):  
Martin Leduc ◽  
Xin Hou ◽  
David Hamel ◽  
Melanie Sanchez ◽  
Christiane Quiniou ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Artery ◽  
Artery Occlusion ◽  
Hek293 Cells ◽  
Heme Oxygenase 1 ◽  
Histological Changes ◽  
Ep4 Receptor ◽  
Renal Artery Occlusion

Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE2 is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP4 receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP4 receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE2-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP4-mediated relaxation of piglet saphenous vein rings, partially inhibited EP4-mediated cAMP production, but did not affect Gαi activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP4-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP4-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP4 receptor, resulting in improved renal function and integrity following acute renal failure.

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