Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postischemic acute renal failure was induced by 1 hr of clamping of the renal vasculature. Adenine nucleotide (ATP, ADP, AMP) and lactate (Lac) levels were measured after 0, 0.25, 1, 6, 24, and 48 hr of reflow to determine the time necessary for recovery to control levels. After 1 hr of ischemia with no reflow, [ATP] was 18% and [Lac] was 10-fold control levels. Control levels were restored after 24 hr of reflow. Variable ischemic times (5, 15, 30, 60, 90, and 120 min) followed by (1) no reflow or (2) 24 hr of reflow were also studied. [ATP] decreased to 25 and 13% of controls after 5 and 120 min of ischemia, respectively, and [Lac] increased to 5- and 13-fold controls after 5 and 120 min. Five to ninety minutes of ischemia followed by 24 hr of reflow resulted in a trend toward restoration of ATP and Lac levels; whereas, 120 min of ischemia followed by 24 hr of reflow resulted in death. The results indicate that: (1) In vivo ischemia results in a drastic and rapid shift in the ATP-ADP-AMP equilibrium; (2) the absolute concentration of ATP is not a reliable criterion of cell viability, but the ability to resynthesize ATP may be determinant in the reversibility of the lesion; (3) 1 hr of ischemia is reversible with respect to restoration of [ATP] and [Lac], but 24 hr of reflow are needed for restoration; and (4) ischemia for 90 min results in a metabolic derangement which is partially reversible in that metabolite levels are partially restored after 24 hr of reflow. However, 90 min of vascular clamping is not functionally reversible since the majority of animals exhibit severe azotemia and do not survive.
Exp Mol Pathol 1984 Apr
PMID:Metabolic studies of postischemic acute renal failure in the rat. 670 89

The two endothelin (ET) receptor subtypes (ETA and ETB) have been characterized in rat kidney from normal rats and rats with acute renal failure induced by hypertonic glycerol administration. In control rats, the total number of ET receptors in kidney cortex and medulla was 155 and 386 fmol/mg of protein, respectively. The ratio of ETA to ETB receptors was 54:46 in renal cortex and 35:65 in renal medulla. Treatment of rats with 10 ml/kg glycerol (50%, w/v) intramuscularly resulted in severe renal dysfunction; the serum urea concentration increased from 0.46 to 2.65 g/liter and the creatinine clearance decreased from 1.06 to 0.30 ml/min. Ligand binding studies showed that glycerol-induced acute renal failure was associated with a marked up-regulation of ETA and ETB receptor subtypes in both cortex and medulla. In glycerol-treated rats, the total ET receptor density in kidney cortex and medulla was increased to 294 and 1172 fmol/mg of protein, with ETA/ETB ratios of 52:48 and 31:69, respectively. The upregulatory effect of glycerol treatment was significantly more pronounced in renal medulla than renal cortex and affected ETB receptors preferentially, compared with ETA receptors. Subsequently, ETA and ETB receptor mRNA levels were markedly increased by glycerol administration in both kidney cortex and medulla, as assessed by polymerase chain reaction coupled to reverse transcription. These results suggest that up-regulation of renal ET receptors, particularly ETB receptors in kidney medulla, may account for or contribute to renal function impairment induced by glycerol, and they support a pathophysiological role for ET in acute renal failure.
Mol Pharmacol 1994 Feb
PMID:Endothelin receptor subtypes A and B are up-regulated in an experimental model of acute renal failure. 811 69

The pharmacokinetic and tissue distribution changes of adriamycin (ADM) and adriamycinol were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control and the uranyl nitrate-induced acute renal failure (U-ARF) rats. After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 hr in the U-ARF rats, whereas the levels were detected for only up to 3 hr in the control rats. Adriamycinol was detected in plasma for up to 180 min for the U-ARF rats, but, it was detected for only up to 1 min for the control rats with significantly higher levels in the U-ARF rats. The mean amount of both ADM and adriamycinol excreted in urine were significantly smaller in the U-ARF rats than those in the control rats due to the decreased kidney function in the U-ARF rats. In tissue distribution studies, the amount of ADM obtained from the heart, liver, spleen, small intestine, large intestine, and fat were significantly higher in the U-ARF rats than those in the control rats. The tissue to plasma ratios of the liver, spleen, large intestine, and fat also increased significantly in the U-ARF rats than those in the control rats. The amount of adriamycinol obtained from the heart, spleen, and liver were significantly higher in the U-ARF rats. All 7 control rats survived over 48 hr whereas 6 out of 8 U-ARF rats died between 36-48 hr after i.v. administration of ADM, suggesting that the i.v. doses of ADM in acute renal failure patients may need modification if the present rat data could be extrapolated to humans.
Res Commun Mol Pathol Pharmacol 1996 Feb
PMID:Pharmacokinetic and tissue distribution changes of adriamycin and adriamycinol after intravenous administration of adriamycin to uranyl nitrate-induced acute renal failure rats. 883 11

The pharmacokinetic changes of methotrexate (MTX) were investigated after 1-min intravenous (iv) administration of MTX, 8 mg/kg, to the control and the uranyl nitrate-induced acute renal failure (U-ARF) rats. The impaired kidney and liver functions were observed by pretreatment with urinary nitrate based on physiological parameters of plasma and urine, and the tissue microscopy. After 1-min iv infusion of MTX, the plasma concentrations of MTX (except at 1 min) and the total area under the plasma concentration-time curves of MTX (542 versus 297 micrograms min/ml) increased significantly in the U-ARF rats when compared to those in the control rats. This was due to the significantly slower in total body clearance (CL) of MTX (15.2 versus 27.5 ml/min/kg) in the U-ARF rats than that in the control rats. The significantly slower in CL of MTX in the U-ARF rats was due to the significantly slower both renal (1.01 versus 8.39 ml/min/kg, because of the considerably decreased renal tubular secretion of MTX) and nonrenal (14.2 versus 19.1 ml/min/kg, because of the considerably decreased liver metabolism) clearances in the U-ARF rats. All 11 control rats survived until sacrificed (24 h), however, 5 out of 15 U-ARF rats died within 7 h after iv administration of MTX. If the present rat data were to be extrapolated to human beings, iv dose of MTX need to be modified in the acute renal failure patients.
Res Commun Mol Pathol Pharmacol 1996 Sep
PMID:Pharmacokinetic changes of methotrexate after intravenous administration to uranyl nitrate-induced acute renal failure rats. 889 46

ADP ribosylation factor (ARF) is thought to play a critical role in recruiting coatomer (COPI) to Golgi membranes to drive transport vesicle budding. Yeast strains harboring mutant COPI proteins exhibit defects in retrograde Golgi to endoplasmic reticulum protein transport and striking cargo-selective defects in anterograde endoplasmic reticulum to Golgi protein transport. To determine whether arf mutants exhibit similar phenotypes, the anterograde transport kinetics of multiple cargo proteins were examined in arf mutant cells, and, surprisingly, both COPI-dependent and COPI-independent cargo proteins exhibited comparable defects. Retrograde dilysine-mediated transport also appeared to be inefficient in the arf mutants, and coatomer mutants with no detectable anterograde transport defect exhibited a synthetic growth defect when combined with arf1Delta, supporting a role for ARF in retrograde transport. Remarkably, we found that early and medial Golgi glycosyltransferases localized to abnormally large ring-shaped structures. The endocytic marker FM4-64 also stained similar, but generally larger ring-shaped structures en route from the plasma membrane to the vacuole in arf mutants. Brefeldin A similarly perturbed endosome morphology and also inhibited transport of FM4-64 from endosomal structures to the vacuole. Electron microscopy of arf mutant cells revealed the presence of what appear to be hollow spheres of interconnected membrane tubules which likely correspond to the fluorescent ring structures. Together, these observations indicate that organelle morphology is significantly more affected than transport in the arf mutants, suggesting a fundamental role for ARF in regulating membrane dynamics. Possible mechanisms for producing this dramatic morphological change in intracellular organelles and its relation to the function of ARF in coat assembly are discussed.
Mol Biol Cell 1998 Mar
PMID:ARF is required for maintenance of yeast Golgi and endosome structure and function. 2284 64

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg) administration to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on the basis of physiological parameters. After intravenous administration of YJA-20379-8, the pharmacokinetic parameters were not significantly different between two groups of rats except significant increase in volume of distribution at steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126 versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8 from gastrointestinal tract; the percentages of oral dose of YJA-20379-8 recovered from gastrointestinal tract at 24 hr as unchanged drug was significantly greater (19.9% versus 6.61%) in rats with U-ARF.
Res Commun Mol Pathol Pharmacol 1998 Oct
PMID:Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure. 992 Mar 45

Effects of propranolol on the pharmacokinetics of cyclosporine were investigated after intravenous and oral administration of the drugs to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). Effects of intravenous propranolol, 3 mg/kg, on the pharmacokinetics of intravenous cyclosporine, 3 and 30 mg/kg, to control rats, and 30 mg/kg, to rats with U-ARF seemed to be negligible. However, the effects of orally administered propranolol, 10 mg/kg, on the area under the blood concentration-time curve (AUC) of oral cyclosporine were significant after oral administration of cyclosporine, 10 and 100 mg/kg, to control rats. For example, the AUC of cyclosporine increased significantly (33.1 versus 24.7 microg h/ml) at cyclosporine oral dose of 10 mg/kg, however, the value decreased significantly (167 versus 235 microg h/ml) at cyclosporine oral dose of 100 mg/kg. Effects of orally administered propranolol, 10 mg/kg, on the pharmacokinetics of orally administered cyclosporine, 100 mg/kg, seemed to be negligible in rats with U-ARF.
Res Commun Mol Pathol Pharmacol 1998 Dec
PMID:Effects of propranolol on the pharmacokinetics of cyclosporine after intravenous and oral administration to control rats and rats with uranyl nitrate-induced acute renal failure. 1034 12

Neutral endopeptidase (NEP, 24.11) is an ectoenzyme involved in the degradation of peptide hormones such as endothelin (ET), atrial natriuretic factor and enkephalins. The current study was designed to assess the involvement of NEP in ischemia-induced acute renal failure (ARF). In unilaterally nephrectomized Sprague-Dawley rats, the left renal artery was occluded for 30 min under pentobarbital anesthesia (40 mg/kg, i.p.) at 37 degree C. In addition to plasma creatinine levels, NEP activity was determined in renal cortical membranes at 0, 2, 5, and 24 h following reperfusion. Plasma creatinine levels significantly increased at 2, 5 and 24 h. There was a significant decrease in NEP activity as early as 2 h following reperfusion that was maintained up to 24 h (57.9 +/- 4%) with a concomitant loss of enzyme protein shown by Western analysis. Northern analysis of kidney cortical RNA, probed with an NEP cDNA, showed a 45% decrease in NEP mRNA level by the end of the ischemic period and decreased further during reperfusion. Thus, decrease in NEP mRNA levels preceded the changes in protein level, enzyme activity and plasma creatinine levels. These data, along with the reported increase in the tissue level of ET in kidney cortex, and the beneficial effect of ET antibody as well as ET receptor antagonist in ARF, suggest that down regulation of NEP, one of the mechanisms leading to increased tissue level of ET, may be a contributing factor to ARF.
Mol Cell Biochem 1999 Jul
PMID:Down regulation of kidney neutral endopeptidase mRNA, protein and activity during acute renal failure: possible mechanism for ischemia-induced acute renal failure in rats? 1048 24

Shiga toxins (Stxs) produced by enterohaemorrhagic Escherichia coli may induce colonic ulceration, bloody diarrhoea and acute renal failure. The A subunit (StxA) is known to inhibit protein synthesis, whereas the B subunits (StxB) bind to Gb3 on the cell surface. However, the mechanisms by which Stxs kill target cells remain unclear. Stx1A or Stx1B genes were introduced into pcDNA3.1 vectors and transfected into NIH3T3 and HeLa cells. The Stx1B gene-transfected cells became apoptotic with accompanying DNA fragmentation, whereas the Stx1A gene-transfected cells were found to be necrotic and no DNA fragmentation occurred. The HeLa/C4 cells integrated with the Stx1B gene with a tetracycline-inducible promoter eventually produced cytoplasmic Stx1B, leading to DNA fragmentation on the addition of doxycycline. These apoptotic changes were abrogated by pretreatment with Z-VAD-fmk. These results suggest that the transfected Stx1B gene induces apoptosis by activating the caspase cascade after Stx1B expression in the cytoplasm.
Mol Microbiol 1999 Sep
PMID:Regulated expression of the Shiga toxin B gene induces apoptosis in mammalian fibroblastic cells. 1051 Feb 33

Many glomerular diseases are associated with changes in the expression and distribution in the components of extracellular matrix. A remarkable feature in acute renal failure induced by mercuric chloride in rats was large fibronectin (Fn) deposits in kidneys 1 h post-HgCl2 injection (5 mg/kg body wt., s.c.). Our study examined some mechanisms as potential explanation of the early Fn deposits in mercuric chloride induced acute renal failure. Total tissue mRNA of livers and kidneys of control and treated rats were used in Northern blot to determine whether accumulation of Fn in kidney is associated with increases in the expression of this protein in the kidney and/or in the liver. Analysis of Fn levels by Western blot were also performed. Northern blot did not show significant difference between control and treated rats, while the abundance of polymerized-Fn in kidney tissue was increased 1 h and 5 h post HgCl2 injection. HgCl2 influence on Fn folding was studied in vitro to detect possible conformational changes that could altered its normal pattern of matrix assembly and/or binding to different ligands. In this context HgCl2 binding to Fn was measured following native tryptophan fluorescence of Fn in the presence of HgCl2 (0.5-250 mM). Binding parameters for the HgCl2-Fn complex formation were Kd = (1.6 +/- 0.2) 10(-4) M; n = 1 +/- 0.3, indicating a low apparent affinity and one type binding site. Thermal denaturation of Fn showed, between 30-60 degrees C, a soft reversible conformational change, while between 75-80 degrees C a highly and irreversible transition is produced suggesting a modification of the tertiary structure. HgCl2 abolished this transition. The kinetic of thermal unfolding of Fn was also measured and the effects observed due to HgCl2 presence reinforced the previous data. Finally, the effect of HgCl2 on Fn binding to denatured collagen (gelatin) was also measured as an index of the effect of this cation on biological properties of Fn. Fn binds gelatin strongest in the presence of HgCl2. Our results suggest that higher Fn deposits in kidney-treated rats seems not to be associated to augmented mRNA-Fn neither in kidney nor in liver. On the other hand, increased levels of polymerized Fn abundance was observed in kidney tissue from mercury-treated rats. We also describe that HgCl2 promotes, in vitro, conformational changes on Fn structure, inducing its denaturation and increasing its binding to gelatin, all events that could be related to the Fn deposits in renal tissues of HgCl2 treated rats, and could be expected in other situations that promoted interstitial fibrosis, not associated to overexpression of matrix-proteins.
Mol Cell Biochem 2001 Oct
PMID:Potential mechanism of fibronectin deposits in acute renal failure induced by mercuric chloride. 1176 40


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