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

In the absence of notable changes in heme metabolic activities in the testes of rats treated with cis-platinum (7 mg/kg i.v.) and sacrificed after 1, 3 or 7 days, time-dependent decreases in the activity of benzo(a)pyrene hydroxylase (AHH), ethoxyresorufin O-deethylase (7-ERDE) and the concentration of cytochrome P-450 were observed. In contrast, in the prostate of the treated rats, despite reductions in the activity of heme oxygenase and that of enzymes of heme biosynthetic pathway, biotransformation of benzo(a)pyrene and ethoxyresorufin and cytochrome P-450 concentration were not altered. cis-Platinum treatment (7 days) also decreased markedly the serum and testicular testosterone levels (50-70%). Human chorionic gonadotropin (hCG, 25 IU/100 g/day for 7 days) given to the treated rats (7 days) caused a 5- to 15-fold increase in the serum and testicular testosterone levels and reversed the spectrum of the aforementioned inhibitory effects of cis-platinum on heme metabolic enzymes. The response of the testis and prostate drug metabolic activities to hCG treatment also differed. In the testis of cis-platinum-treated rats, the inhibited AHH and 7-ERDE activities were reversed by hCG treatment and cytochrome P-450 concentration returned to the control level. In the prostate, however, hCG treatment neither changed AHH and 7-ERDE activities nor the concentration of the microsomal cytochrome P-450. In addition, in the testis the pattern of response of AHH and 7-ERDE activities to hCG was dissimilar; whereas 7-ERDE activity returned to the normal level, AHH activity surpassed the normal activity and reached a near 2.5-fold increase over the control value.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential regulation of heme and drug metabolism in rat testis and prostate: response to cis-platinum and human chorionic gonadotropin. 232 24

A radioimmunoassay was developed to assess the response of testicular HO-1 to agents known to increase the microsomal heme oxygenase activity. Treatment of rats with human chorionic gonadotropin (hCG) increased the microsomal heme oxygenase activity in rat testis. The following data suggest that the increase was specific to the HO-1 isozyme: (a) The elution profile of heme oxygenase activity from a DEAE-Sephacel column showed an increase in the HO-1 peak, but not in the HO-2 peak, (b) the Western immunoblot of the testis microsomes showed an increase in HO-1 protein, and (c) the amount of HO-1 protein that was present in the microsomes, when measured by radioimmunoassay, was doubled. Using radioimmunoassay, it was shown that other agents known to increase the testicular heme oxygenase, sodium arsenate and sodium arsenite, also increased the microsomal content of HO-1. An inhibitor of the testicular microsomal heme oxygenase activity, cadmium, also increased the microsomal HO-1 protein. The findings suggest that inducibility of HO-1 extends to tissues other than the liver, in this instance, the testis, and further support the possibility that HO-1 is the only inducible form of heme oxygenase.
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PMID:Selective induction of heme oxygenase-1 isozyme in rat testis by human chorionic gonadotropin. 291 70

Repeated administration of human chorionic gonadotropin to rats results in a maximal depression of testicular microsomal heme and cytochrome P-450 levels at 24 h, followed by increases that plateau at pretreatment levels by day six. Associated with the depressed levels of microsomal heme and cytochrome P-450 is an increase of testicular microsomal heme oxygenase activity at 12-24 h. Testicular mitochondrial delta-aminolevulinic acid synthase activity was increased at 24 h, and remained elevated throughout the 9-day treatment period. Pretreatment with 1,4,6-androstatrien-3,17-dione, an aromatase inhibitor, failed to prevent the depression of testicular microsomal heme or cytochrome P-450 or increased heme oxygenase activity caused by repeated administration of human chorionic gonadotropin, and administration of estradiol benzoate failed to alter testicular microsomal heme oxygenase activity suggesting that these parameters were not related to altered testicular estrogen content caused by increased aromatase activity. These results suggest that increased testicular heme oxygenase activity is associated with decreased microsomal heme and cytochrome P-450 content during human chorionic gonadotropin-induced desensitization.
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PMID:Increased rat testicular heme oxygenase activity associated with depressed microsomal heme and cytochrome P-450 levels after repeated administration of human chorionic gonadotropin. 348 41

The treatment of rats with cis-platinum for 7 days caused a profound, and seemingly selective, decrease (70-80%) in the microsomal cytochrome P-450 levels in the testis. This decrease was accompanied by marked reductions (70-80%) in steroid 17 alpha-hydroxylase activity and in plasma testosterone concentration. The treatment of rats with human chorionic gonadotropin partially restored the cytochrome P-450 concentration and 17 alpha-hydroxylase activity and permitted the plasma testosterone level to approach control values. The effect of cis-platinum on the testicular cytochrome P-450 appeared unrelated to deficiencies in heme metabolic processes, in so far that neither was the activity of delta-aminolevulinate synthetase decreased, nor was that of heme oxygenase increased. These enzymes are rate-limiting in heme biosynthesis and degradation pathways, respectively. Also, the activities of uroporphyrinogen I synthetase, delta-aminolevulinate dehydratase, and ferrochelatase and the concentration of total porphyrins in the testis remained unchanged. The sodium dodecyl sulfate-gel electrophoresis of the microsomal preparation did not reveal a diminished level of apocytochrome; however, in this preparation, heme could not be detected in molecular weight regions corresponding to cytochrome P-450. The microsomal cytochrome b5 and the mitochondrial heme concentrations were not decreased in cis-platinum-treated rats. It is suggested that the mechanism of depletive action of cis-platinum on microsomal cytochrome P-450 involves an impairment of the effective assembly of heme and apoprotein moieties. It is further suggested that the anterior pituitary hormones control the factor(s) involved in this assembly, a process which is interrupted by cis-platinum.
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PMID:Inhibition of testicular cytochrome P-450-dependent steroid biosynthesis by cis-platinum. Reversal by human chorionic gonadotropin. 403 24

A novel action of the gonadotropic hormones of the adenohypophysis on the regulation of kidney heme metabolism and cytochrome P-450 concentrations is described. The treatment of rats with cis-platinum for 7 days caused a greater than twofold increase in the microsomal cytochrome P-450 and heme concentrations in the kidney. The sodium dodecyl sulfate-gel electrophoresis of the microsomal preparation revealed increased levels of both apocytochrome P-450 and heme in the molecular weight region corresponding to cytochrome P-450. In hypophysectomized rats, similar increases in heme and the cytochrome contents in the kidney were observed. Conversely, the treatment of rats with human chorionic gonadotropin (hCG) fully reversed the effect of cis-platinum on heme and cytochrome P-450 concentrations. The cellular basis of increases in concentrations of heme and the hemoprotein was explored by measuring the incorporation of [14C]glycine-labeled hemoglobin heme into the kidney microsomal heme fractions. In comparison with the control rats, the specific 14C activity of heme in microsomal fraction was not increased. Moreover, the effect of cis-platinum on kidney cytochrome P-450 appeared to be unrelated to alterations in the activities of the rate-limiting enzymes of heme biosynthesis and degradation pathways, delta-aminolevulinate synthetase, and heme oxygenase, respectively. On the other hand, ferrochelatase activity and the concentration of total porphyrins in the kidney were profoundly altered by cis-platinum treatment; a twofold increase in ferrochelatase activity and a marked reduction (40%) in the total porphyrin concentration were observed. Also, the activities of uroporphyrinogen-I synthetase and delta-aminolevulinate dehydratase were decreased in cis-platinum-treated animals. The latter effects reflect a direct inhibitory action of cis-platinum. It appears that the cis-platinum-mediated increase in the microsomal heme concentrations involves an accelerated rate of heme production as a consequence of increased ferrochelatase activity. This, in turn, could increase the production of cytochrome P-450. It is suggested that the anterior pituitary hormones control the concentration of the cytochrome P-450 in the kidney, and this process may be interrupted by cis-platinum.
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PMID:Effect of cis-platinum on kidney cytochrome P-450 and heme metabolism: evidence for the regulatory role of the pituitary hormones. 404 Mar 50

In the rat testis, 7 days after hypophysectomy, the microsomal content of cytochrome P-450 decreased to a negligible level. The sodium dodecyl sulfate gel electrophoresis of the microsomal preparation did not reveal a decrease in apocytochrome P-450; however, in this preparation, heme was undetectable. The latter did not reflect decreases in the activities of the heme biosynthesis enzymes. Also, an increase in heme oxygenase activity did not appear responsible for the suppression of the cytochrome levels. The cellular basis for the depression of the cytochrome was explored by measuring the incorporation of [14C]delta-aminolevulinate into the testicular microsomal and mitochondrial hemoproteins, and determining the relative affinity of microsomal heme for the endoplasmic reticulum membranes. In comparison with the sham-operated animals, in hypophysectomized rats, the specific 14C activity of heme in mitochondrial fraction was not decreased; however, that of the microsomal fraction was markedly reduced. The latter appeared to reflect a lowered binding affinity of the apoprotein moiety of cytochrome P-450 for heme. The treatment of hypophysectomized rats with human chorionic gonadotropin partially restored the normal level of the cytochrome. It is suggested that the anterior pituitary hormones control the level of cytochrome P-450 in the testis through factors which do not involve the production of heme; rather, the control appears to involve the processes of assembly of the hemoprotein and the association of the heme molecule with the apoprotein.
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PMID:Dissociation of heme metabolic activities from the microsomal cytochrome P-450 turnover in testis of hypophysectomized rats. 674 60