Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The time-course and dose-effect relationships for 63Ni uptake in renal parenchyma and nuclei were delineated in 63NiCl2-treated rats, based upon isolation of renal nuclei by sucrose gradient centrifugation and measurements of 63Ni by liquid scintillation counting. In 5 groups of rats killed 2 to 24 hours after 63NiCl2 injection (36 mumol/kg, im), 63Ni content of renal parenchyma (mean +/- SD) diminished from 3.0 +/- 0.3% of the dose at 2 hours to 0.9 +/- 0.3% of the dose at 24 hours; nuclear 63Ni content diminished from 10.5 +/- 4.4 pmol/10(6) nuclei at 2 hours to 3.0 +/- 0.3 pmol/10(6) nuclei at 24 hours. In 8 groups of rats killed 2 hours after injection of 63NiCl2 at dosages from 3 to 250 mumol/kg, 63Ni concentrations in renal nuclei increased progressively from 1.1 +/- 0.3 pmol/10(6) nuclei at 3 mumol/kg to 32.1 +/- 1.7 pmol/10(6) nuclei at 250 mumol/kg. Nuclear 63Ni content generally averaged 1.9 to 2.4% of total renal 63Ni; significantly higher mean values (3.4 +/- 1.0%) were observed in rats killed 48 hours after 5 daily injections of 63NiCl2 (1.1 mumol/kg/day). Combined administration of diethyldithiocarbamate (DDC, 1.33 mmol/kg, im) and 63NiCl2 (36 mumol/kg, im) increased 63Ni uptake in renal nuclei (4.8 +/- 1.4% of renal 63Ni; P less than 0.05 versus corresponding value of 2.0 +/- 0.2% in rats that received 63NiCl2, alone). Enhanced nuclear uptake of 63Ni evidently explains the synergistic effect of DDC and NiCl2 on induction of heme oxygenase activity in rat kidney.
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PMID:63Ni content of renal parenchyma and nuclei from 63NiCl2-treated rats. 299 86

The experimental data that have been reviewed support the following conclusions regarding metal induction of microsomal heme oxygenase activity: 1. Induction of heme oxygenase in liver, kidney, and other organs of rodents is a nonspecific, toxic response to parenteral administration of numerous metal compounds. 2. The Co2+ and Cd2+ ions are especially potent for induction of heme oxygenase in rat liver; Sn2+, Ni2+, and As3+ are especially potent for induction of the enzyme in rat kidney; Hg2+ is especially potent for induction of the enzyme in rat adrenal. 3. Rat spleen, testis, and brain are relatively refractory to metal induction of heme oxygenase activity; in testicular microsomes from Cd2+-treated rats, heme oxygenase activity is markedly inhibited. 4. Metal induction of heme oxygenase requires de novo synthesis of mRNA and protein, based on 1) experiments with metabolic inhibitors (actinomycin D, puromycin, and cycloheximide) and 2) translation assays of heme oxygenase mRNA. 5. Heme oxygenase induction by metals is generally suppressed by treatments with SH compounds (for example, cysteine and glutathione) and enhanced by agents that deplete tissue SH levels (for example, diethyl maleate), suggesting that the induction mechanism may involve binding of metal ions to SH-containing regulatory molecules. 6. Administration of DDC exerts a pronounced synergistic effect on Ni2+ induction of heme oxygenase activity in rat tissues, attributable in part to enhanced cellular uptake of nickel. 7. Induction of heme oxygenase is not sustained during repeated daily treatments of rats with NiCl2, pointing to an adaptive mechanism for tolerance to the enzyme inducer. Investigations of metal induction of heme oxygenase activity have commonly involved sc or ip administration of the test compounds to rats. The paucity of studies in other species and the dearth of experiments with oral or respiratory exposures hinder extrapolations of the animal data to human environmental or occupational exposures to metal compounds.
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PMID:Metal induction of heme oxygenase. 332 38

Heme oxygenase activity was measured in tissues of rats killed after administration of NiCl2 or Ni3S2. Induction of renal heme oxygenase activity occurred 6 hr after NiCl2 injection (0.25 mmol/kg, sc), reached a maximum of five to six times the baseline activity at 17 hr, and remained significantly increased at 72 hr. Heme oxygenase activities were also increased in liver, lung, and brain at 17 hr after the NiCl2 injection; heme oxygenase activities in spleen and intestinal mucosa were unchanged. The effects of NiCl2 on heme oxygenase activities in kidney and liver were dose-related from 0.06 to 0.75 mmol/kg, sc. Three Ni chelators were administered (1 mmol/kg, im) prior to injection of NiCl2 (0.25 mmol/kg, sc); d-penicillamine partially prevented Ni induction of renal heme oxygenase activity; triethylenetetramine had no effect; sodium diethyldithiocarbamate enhanced the Ni induction of renal heme oxygenase activity (three times greater than NiCl2 alone). Intrarenal injection of Ni3S2 (10 mg/rat) caused induction of renal heme oxygenase activity at 1 week but not at 2, 3, or 4 weeks; no correlation was observed between induction of renal heme oxygenase activity and erythropoietin-mediated erythrocytosis. Hypoxia (10% O2, 12 hr/day, 7 days) did not affect renal heme oxygenase activity. Induction of renal heme oxygenase activity was observed in mice, hamsters, and guinea pigs killed 17 hr after injection of NiCl2 (0.25 mmol/kg, sc). These studies established (a) the time course, dose-effect, organ selectivity, and species susceptibility relationships for Ni induction of microsomal heme oxygenase activity, (b) the effects of Ni chelators, and (c) the lack of relationship between induction of renal heme oxygenase activity and the erythrocytosis that develops after intrarenal injection of Ni3S2.
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PMID:Nickel induction of microsomal heme oxygenase activity in rodents. 630 52

Microsomal heme oxygenase activity was measured in liver and kidney of rats killed after administration of sodium diethyldithiocarbamate (DDC) and nickel chloride (NiCl2), singly and in combinations (DDC dosages: 0.33 to 1.33 mmol/kg, im, 17 hr before death; NiCl2 dosages: 0.125 and 0.25 mmol/kg, sc, 17 hr before death). Synergistic induction was observed at all dosage combinations. At the highest dosages of DDC and NiCl2, the dual treatments induced heme oxygenase activity 11-fold in liver and 16-fold in kidney; at the same dosages given individually, DDC induction of heme oxygenase activity was 3-fold in liver and 2-fold in kidney, and NiCl2-induction was 1.3-fold in liver and 6-fold in kidney. Synergistic induction of heme oxygenase activity in liver occurred when DDC was injected 6 hr before to 6 hr after NiCl2; synergistic induction in kidney occurred when DDC was injected 6 hr before to 3 hr after NiCl2. Actinomycin D prevented the induction of heme oxygenase activity by DDC or NiCl2, given individually; the effect of actinomycin D on synergistic induction could not be measured, since the rats all died following treatment with DDC, NiCl2, and actinomycin D. Administration of cysteine to rats, po, 18 hr before death, partially suppressed the induction of hepatic heme oxygenase activity by DDC, singly or in combination with NiCl2. Synergistic induction of hepatic heme oxygenase activity also occurred in rats that received dual injections of DDC (1.33 mmol/kg, im) and hemoglobin (0.3 g/kg, iv); the synergism of DDC and hemoglobin, although statistically significant, was small in comparison to the striking synergistic effect of DDC and NiCl2.
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PMID:Synergistic induction of microsomal heme oxygenase activity in rat liver and kidney by diethyldithiocarbamate and nickel chloride. 631 91

Concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) and 4 trace metals (Ni, Cu, Mn, Zn) were measured in livers from rats treated with sodium diethyldithiocarbamate (DDC, 0.67 or 1.33 mmol/kg, i.m.) and NiCl2 (0.25 or 0.50 mmol/kg, s.c.), singly or in combination. In rats treated with DDC or NiCl2, singly, hepatic GSH was diminished at 4 h and returned to control levels (or slightly above) at 17 h. In rats that received DDC plus NiCl2, hepatic GSH was not diminished at 4 h after increased 1.4-1.8-fold at 17 h. Hepatic GSSG was diminished at 4 h after NiCl2 treatment and returned to control values at 17 h; hepatic GSSG did not differ from control values at 4 h or 17 h after treatment with DDC, alone or combined with NiCl2. Hepatic Ni was below the detection limit (approximately 20 nmol/g) in control and DDC-treated rats; hepatic Ni was increased to 53 +/- 26 (S.D.) nmol/g at 17 h after treatment with NiCl2 alone, and was increased 6-fold (308 +/- 63 nmol/g) in rats that received Ni plus DDC. Under the same conditions, hepatic Zn was increased 33% or 41%, respectively, in rats that received NiCl2 or DDC, singly, and was not further increased by combined treatment; hepatic Cu and Mn concentrations were unaffected by NiCl2 or DDC, singly, but were diminished in rats that received NiCl2 and DDC. This study suggests: (a) that increased hepatic uptake of Ni is largely responsible for the synergistic induction of heme oxygenase activity in rats treated with NiCl2 and DDC; and (b) that increased hepatic uptake of Zn contributes to the induction of hepatic metallothionein by NiCl2 and DDC.
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PMID:Effects of diethyldithiocarbamate and nickel chloride on glutathione and trace metal concentrations in rat liver. 633 Sep 38

We have developed an improved assay for microsomal heme oxygenase activity, based on the enzymic release of CO from the alpha-methene bridge of hemin and the quantitation of CO by gas chromatography. The within-run coefficient of variation (CV) of heme oxygenase assays in microsomes from rat tissues (liver, kidney) averaged 8%; the between-run CV averaged 15%. The detection limit for heme oxygenase activity was approximately 1 nmol/h per milligram of microsomal protein. Gas-chromatographic assays of heme oxygenase activities in rat tissues correlated well (r = 0.94) with results by a spectrophotometric assay based on bilirubin production. In untreated rats, heme oxygenase activity averaged 7 +/- 3 nmol/h per milligram of protein (n = 36) in kidney microsomes and 14 +/- 5 nmol/h per milligram of protein (n = 17) in liver microsomes. Heme oxygenase activity was increased 10-fold in kidney microsomes and threefold in liver microsomes from rats killed 17 h after subcutaneous injection of NiCl2 (0.5 mmol/kg body wt). These findings illustrate the efficacy of the gas-chromatographic assay for measuring xenobiotic effects on heme oxygenase activity.
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PMID:Gas-chromatographic assay for heme oxygenase activity. 689 23