Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The hepatopancreas is the major site of cytochrome P450-dependent xenobiotic monooxygenation in crustacean species, but the presence of monooxygenase inhibitors in hepatopancreas microsomes and cytosol from many decapod species has impeded in vitro studies. Cytochrome P450 and monooxygenase activities have been reported in other crustacean organs including the antennal gland (green gland) and stomach. 2. NADPH cytochrome c reductase activity is often very low (typically less than 10 nmol cytochrome c reduced/min per mg microsomal protein) in hepatopancreas microsomes from crustacean species. NADPH cytochrome P450 reductase activity has not yet been detected in crustacean hepatopancreas microsomes. 3. The cytochrome P450 present in hepatopancreas of several crab species and the spiny lobster has been resolved into several fractions by chromatography on DEAE-cellulose. One form of cytochrome P450 from spiny lobster has been purified to 12 +/- 2 nmol/mg protein. 4. Reconstitution studies with spiny lobster hepatopancreas P450 have shown that the vertebrate sex steroids, progesterone and testosterone, are excellent substrates, whereas ecdysone--the crustacean molting hormone--is not a substrate. Activity was found with several xenobiotic substrates including benzphetamine, aminopyrine, benzo(a)pyrene, ethyl-, benzyl- and pentyl-phenoxazones and ethoxycoumarin. Highest activities (greater than 50 nmol/min per nmol P450) were found for N-demethylation of benzphetamine and aminopyrine. 5. The ability of agents which induce vertebrate cytochrome P450 to induce cytochrome P450 in crustaceans is still unclear. Some studies indicate that polycyclic aromatic hydrocarbons, but not phenobarbital-type inducers, could induce cytochrome P450 in crustaceans, whereas other studies showed no effect of either inducer type. Crustaceans are not as sensitive as fish to induction of P450 and monooxygenase activity.
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PMID:Cytochrome P450 monooxygenases in crustaceans. 268 9

Renal cortical metabolism of drugs and xenobiotics was assessed with microsomes prepared from normal, contralateral and 4-day postobstructive hydronephrotic kidneys. Microsomal mixed-function oxidase and prostaglandin H synthase systems were determined in control and 3-methylcholanthrene-treated rabbits. Cytochrome P450 content and biphenyl-4-hydroxylase activity but not cytochrome c reductase activity were reduced in the hydronephrotic kidney. 3-Methylcholanthrene treatment increased cytochrome P450 content and biphenyl-4-hydroxylase and acetanilide-4-hydroxylase activities in normal, contralateral, and hydronephrotic kidneys. However, even after 3-methylcholanthrene treatment, hydronephrotic kidney cytochrome P450 content and acetanilide-4-hydroxylase activity were not more than 20% of the corresponding normal kidney values. Prostaglandin H synthase metabolism of benzidine was observed in the hydronephrotic kidney but was at the limit of detection in normal or contralateral kidneys with or without 3-methylcholanthrene treatment. Characteristics of benzidine metabolism were consistent with the hydroperoxidase rather than the fatty acid cyclooxygenase activity of prostaglandin H synthase. Therefore, hydronephrosis alters the drug and xenobiotic metabolic profile of the renal cortex from a primarily mixed-function oxidase-dependent system to one with the potential for metabolism by the hydroperoxide component of prostaglandin H synthase.
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PMID:Renal cortical drug and xenobiotic metabolism following urinary tract obstruction. 643 98

We have discovered cytochrome P450 and associated monooxygenase activities in microsomes prepared from spinal cord tissues from rats and a human. Cytochrome P450 levels and nicotinamide adenine dinucleotide phosphate cytochrome c reductase activities in microsomes from rat spinal cord were similar to those observed from the whole brain. However, certain monooxygenase activities were significantly lower in the rat spinal cord microsomes as compared to the corresponding activities observed in the whole brain. Cytochrome P450-mediated monooxygenase activities were also detectable in microsomes prepared from human spinal cord. Immunoblot analyses of rat and human spinal cord microsomes using antisera to various forms of hepatic cytochrome P450 namely (2B1 + 2B2), 1A1, 1A2 and 2E1 revealed the presence of immunologically similar forms. The spinal cord microsomes also cross-reacted with the antiserum to the phenobarbital-inducible form of rat brain cytochrome P450. Immunocytochemical stain was predominant in the gray horns of the rat spinal cord. At the cervical level, lamina 1 and 2 representing the substantia gelatinosa were intensely stained. In the ventral horns, lamina 7, 8 and 9 containing the large motor neurons were strongly labelled, while small neurons revealed variable staining. In the white matter, the glial cells were stained but the axons remained non-reactive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytochrome P450 and associated monooxygenase activities in the rat and human spinal cord: induction, immunological characterization and immunocytochemical localization. 747 69

There have been considerable interlaboratory variations in the reported levels of rat brain microsomal cytochrome P450 and associated monooxygenase activities. To ascertain if the variability could be accountable, at least in part, to different methodologies used for microsome preparation, cytochrome P450 monooxygenase components and activities were directly compared herein using brain microsome prepared by various methods. Rat brain microsome isolated using a calcium aggregation method in the presence of dithiothreitol and glycerol contained approximately 100 pmol of cytochrome P450/mg protein. Considerably lower cytochrome P450 levels (e.g. 20-40 pmol/mg protein) were found in brain microsome prepared in a more conventional manner using Tris or phosphate buffers without glycerol and dithiothreitol. The NADPH cytochrome c reductase activity was consistently approximately 23-25 nmol of cytochrome c reduced/min/mg protein, whatever the method of preparation of the brain microsome. Cytochrome P450-associated monooxygenase activities, namely morphine N-demethylase and ethoxycoumarin O-deethylase, were dependent on the amount of protein in the incubation medium, the length of incubation, and the ratio of the concentration of the substrate to the amount of protein in the incubation mixture. The specific activity of morphine N-demethylase was constant over a range of protein concentration, if the ratio of the concentration of the substrate to the protein was kept constant.
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PMID:Rat brain cytochrome P450. Reassessment of monooxygenase activities and cytochrome P450 levels. 758 47

An antibody to cytochrome P450 oxidoreductase, purified from rat liver, has been used for the immunohistochemical localization of cytochrome P450 oxidoreductase-like immunoreactivity in the rat central nervous system. The distribution of this immunoreactivity has been confirmed using in situ hybridization with specific cytochrome P450 oxidoreductase antisense DNA probes. Cytochrome P450 oxidoreductase immunoreactivity was detected in neurons and was found in some glial populations. Immunoreactivity and in situ messenger RNA signals were present in many forebrain areas including the olfactory bulb, in the cerebral cortex, caudate-putamen, globus pallidus, hypothalamus, thalamus and hippocampus. Cytochrome P450 oxidoreductase was also detected in the nucleus of the posterior commissure, superior colliculus, intermediate gray layer, periaqueductal gray and in the molecular, Purkinje and granular layers of the cerebellum. In the brain stem, cytochrome P450 oxidoreductase was detected in the substantia nigra, nucleus locus coeruleus and raphe nucleus. Western blotting studies revealed the brain immunoreactive protein has a mol. wt of approximately 72,000, as reported for cytochrome P450 oxidoreductase purified from rat brain microsomes. The distribution of cytochrome P450 oxidoreductase immunoreactivity was compared with the distribution of cells exhibiting NADPH diaphorase activity, which has been established as a histochemical marker for neuronal nitric oxide synthase, an enzyme which has a C-terminus with some structural similarity with cytochrome P450 oxidoreductase and catalyses a complex reaction resulting in the synthesis of nitric oxide from arginine. In general, cytochrome P450 oxidoreductase immunoreactivity and nitric oxide synthase diaphorase activity did not co-localize; however, some neuronal populations did express nitric oxide synthase and exhibit cytochrome P450 oxidoreductase immunoreactivity. Results of immunohistochemistry and in situ hybridization experiments suggest cytochrome P450 oxidoreductase is widespread in the rat central nervous system. The distribution pattern of cytochrome P450 oxidoreductase did not match with those of any one neurotransmitter; however, it did coincide with some brain regions known to harbour central catecholaminergic neurons. The general distribution of cytochrome P450 oxidoreductase was similar to the distribution reported for haeme oxygenase 2 and several cytochrome P450 enzymes. It is possible that malfunctions in cytochrome P450 enzyme systems and/or the haeme oxygenase 2 pathways, both of which involve cytochrome P450 oxidoreductase, may have implications in neurodegenerative diseases.
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PMID:Localization of NADPH cytochrome P450 oxidoreductase in rat brain by immunohistochemistry and in situ hybridization and a comparison with the distribution of neuronal NADPH-diaphorase staining. 796 13

Mixed-function oxygenase (MFO) system components (cytochrome P450 and b5, "423 peak" and NADPH cytochrome c reductase) and body burdens of polycyclic aromatic hydrocarbons (PAHs) were determined seasonally in oysters, Crassostrea virginica (Gmelin 1791), collected from an undeveloped estuary (North Inlet, SC) and an urbanized estuary (Murrells Inlet, SC). All MFO system components monitored in oysters from North Inlet demonstrated seasonal variations; levels were lowest during October 1992. Whole oyster PAH tissue levels were always higher in Murrells Inlet oysters compared with North Inlet oysters. Seasonal variation of PAH body burdens was evident in oysters from Murrells Inlet; the highest levels occurred during April 1993. Differences between the two estuaries were seasonally evident in most oyster MFO system components. Reductase activity was highest at the most contaminated Murrells Inlet site during October 1992 and April 1993. This seasonal variation was positively correlated to that of their PAH body burdens. Cytochrome P450 content was also elevated at the most contaminated site during April 1993. These results suggest that reductase activity and cytochrome P450 content in Murrells Inlet oysters were induced by the high PAH body burdens during April 1993 and indicate their potential as molecular biomarkers of PAH contamination.
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PMID:Seasonal responses of the mixed-function oxygenase system in the American oyster, Crassostrea virginica (Gmelin 1791), to urban-derived polycyclic aromatic hydrocarbons. 883 82

Cytochrome P450 (P450) content and P450-mediated mono-oxygenase activities were measured in microsomes prepared from various regions of rat brain. The regional P450 content in brain varied between 0.1 and 0.15 nmol/mg of protein, with the brainstem and cerebellum showing the highest levels. NADPH cytochrome c reductase activity was highest in the cortex followed by cerebellum and brainstem as compared with the whole brain. Mono-oxygenase activities also varied among the various brain regions. Southern blot analysis of the cDNA synthesized from the poly(A)RNA isolated from rat brain regions and hybridized with cDNA to rat liver P4502B or P4502E1 revealed the presence of a transcript in untreated rat brain that had a molecular mass similar to that of the corresponding transcript from rat liver. Immunoblot analyses using antisera to purified rat liver P4502E1, P450(2B1/2B2), and a phenobarbital-inducible form of rat brain P450 revealed the presence of corresponding immunoreactive protein bands in all the brain regions examined. The present study demonstrated the diversity in the distribution of P450 and associated mono-oxygenase activities in brain and thus may reflect the differential capability of various regions of the brain to detoxify or bioactivate diverse xenobiotics.
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PMID:Expression of multiple forms of cytochrome P450 and associated mono-oxygenase activities in rat brain regions. 974 75

The ecotoxicological effects of mining effluents is coming under much greater scrutiny. It appears necessary to explore possible health effects in association with iron ore mining effluents. The present results clearly demonstrate that iron-ore leachate is not an inert media but has the potential to induce lipid peroxidation. Peroxidation was assessed by measuring oxygen consumption in the presence of a reducing agent such as ascorbate or NADPH and a chelator such as EDTA. Labrador iron ore is an insoluble complex crystalline material containing a mixture of metals (Fe, Al, Ti, Mn, Mg,ellipsis, ) in contrast to the iron sources used for normal lipid peroxidation studies. The metal of highest percentage is iron (59. 58%), a metal known to induce oxyradical production. Iron ore powder initiated ascorbic acid-dependent lipid peroxidation (nonenzymatic) in liposomes, lipids extracted from rat and salmon liver microsomes, and intact salmon liver microsomes. It also revealed an inhibitory effect of NADPH-dependent microsomes lipid peroxidation as well as on NADPH cytochrome c reductase activity. However, nonenzymatic peroxidation in rat liver microsomes was not significantly inhibited. Cytochrome P450 IA1- and IIB1-dependent enzymatic activities as well as P450 levels were not affected. The inhibition could be due to one of the other components of iron ore leachate (Mn, Al,ellipsis, ). These effects of iron-ore leachate indicate that a potential toxicity could be associated with its release into lakes. Further studies are necessary to explore in vivo effects on aquatic animals.
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PMID:Iron ore mines leachate potential for oxyradical production. 1083 36

Normal and imposex-affected female Buccinum undatum were sampled from the open North Sea at three locations, one with low, and two with high shipping densities. Cytochrome P450 components and P450 aromatase activity were determined in the microsomal fractions isolated from pooled digestive gland/gonads. Cytochrome P450 aromatase activity was significantly higher (P < 0.05) in normal females collected in the low shipping density area (1,325 +/- 295 fmol/h/mg protein) than levels from imposex animals from a high shipping density area (620 +/- 287 fmol/h/mg protein). A negative correlation was found between aromatase activity and organotin body burden (r = -0.99). Levels of CYP450, cytochrome b5 and NADPH cytochrome c reductase activity did not show differences among groups. This is the first field evidence of depressed aromatase activity in imposex affected females, although additional research under laboratory controlled conditions is required to fully understand the mechanisms underlying the development of imposex in this species.
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PMID:Cytochrome P450 differences in normal and imposex-affected female whelk Buccinum undatum from the open North Sea. 1240 32

The effects of two-thirds partial hepatectomy on bile acid metabolism have not been well established. This study investigated the changes in microsomal enzymes activities during liver regeneration. The cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-dehydrogenase) activities in male Wistar rats were determined using high-performance liquid chromatography (HPLC). Cytochrome P450 (P450) and cytochrome b5 (b5) levels and NADPH cytochrome c reductase activities were also determined after hepatectomy. 7alpha-Hydroxylase activities were not reduced on days 3, 5, or 7 compared to those of sham-operated rats, but there was a significant decrease (by 60%) of 3beta-dehydrogenase activity compared to that of sham-operated groups (p <0.01) on days 3, 5, and 7 after hepatectomy. While 7alpha-hydroxylase activity had recovered by day 3 after hepatectomy, 3beta-dehydrogenase activity had not, even on day 7. These results suggest that the mechanisms of regulation of these 2 bile acid metabolizing enzymes are significantly different during liver regeneration.
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PMID:Bile acid biosynthesis during liver regeneration: enzyme activities of cholesterol 7alpha-hydroxylase and 3beta-hydroxy-delta5-C27-steroid dehydrogenase in rats. 1608 91


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