Regulation of cytochrome P-450. Immunochemical quantitation of eight isozymes in liver microsomes of rats treated with polybrominated biphenyl congeners.

Dannan, Ghazi A.; Guengerich, F. Peter; Kaminsky, Laurence S.; Aust, Steven D.

doi:10.1016/s0021-9258(18)33190-9

Cited by 131 publications

(16 citation statements)

References 35 publications

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“…a minor form comprising only 129c of the total P450 in MC-microsomcs. whereas P450 IAI can account for the observed changes as it constitutes 569t of the total P450 in these microsomcs < Dannan et al. 1983).…”

Section: Resultsmentioning

confidence: 95%

“…The different forms of P4501 exhibit unique catalytic activity profiles toward various substrates. In particular, the 3-methylcholanthrene (MC) inducible 1A1 form, which is the major P450 in the livers of rats treated with MC (Thomas et al, 1981;Dannan et al, 1983), has been extensively studied. This P450 efficiently metabolizes polycyclic aromatic hydrocarbons (PAHs) (Ryan et al, 1982) to a variety of products, including activated metabolites that covalently bond to cellular macromolecules and may initiate carcinogenesis (Conney, 1982, and references cited therein).The carcinogenicities of numerous PAHs have been evaluated and related to their structures (Arcos & Argus, 1974;Wislocki & Lu, 1988;Harvey, 1991).…”

mentioning

confidence: 99%

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Interaction of Polycyclic Aromatic Hydrocarbons and Flavones with Cytochromes P450 in the Endoplasmic Reticulum: Effect on CO Binding Kinetics

Koley¹,

Robinson²,

Markowitz³

et al. 1995

Biochemistry

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The flash photolysis technique was used to examine the kinetics of CO binding to cytochromes P450 in rat liver microsomes. The effect of polycyclic aromatic hydrocarbons (PAHs) and flavones was used to distinguish the kinetic behavior of the PAH-metabolizing P450 1A1 from that of the remaining multiple microsomal P450s. Applying this approach to microsomes from 3-methylcholanthrene-treated rats showed that although all tested PAHs accelerated CO binding to P450 1A1, the extent varied markedly for different PAHs. The tricyclic PAHs phenanthrene and anthracene enhanced CO binding by 37- and 49-fold, respectively, while several tetracyclic and pentacyclic PAHs increased the rate by 3-16-fold. The results indicate that PAHs exert a dual effect on the rate of CO binding to P450 1A1: a general enhancement via widening of the CO access channel and a reduction that is dependent on PAH size. Although 5,6-benzoflavone increased the rate of CO binding to P450 1A1 by 3.5-fold, it additionally decelerated binding to a constitutive P450 by 15-fold. This flavone thus exerts markedly different effects on two P450s within the same microsomal sample. In contrast, the sole effect of 7,8-benzoflavone was acceleration of CO binding to P450 1A1 by 18-fold. The divergent effects of these isomeric flavones, which only differ in positioning of an aromatic ring, illustrate the sensitivity of CO binding to substrate structure. The varying effects of these PAHs and flavones on CO binding kinetics show that they differentially modulate P450 conformation and access of ligands to the P450 heme and demonstrate that binding of carcinogens to a specific target P450 can be evaluated in its native microsomal milieu.

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Section: Resultsmentioning

confidence: 95%

mentioning

confidence: 99%

Interaction of Polycyclic Aromatic Hydrocarbons and Flavones with Cytochromes P450 in the Endoplasmic Reticulum: Effect on CO Binding Kinetics

Koley¹,

Robinson²,

Markowitz³

et al. 1995

Biochemistry

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“…Like other toxic halogenated aromatics, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Poland and Knutson, 1982; Poland and Glover, 1980), commercial PBBs cause weight loss, thymic atrophy, liver damage, endocrine disorders, and various skin lesions in exposed animals (Gupta and Moore, 1979;Gupta et al, 1981Gupta et al, , 1983a. Commercial PBBs are also potent inducers of a variety of drug-metabolizing enzymes, including several forms of cytochrome P-450 (Dent et al, 1976(Dent et al, ,1977(Dent et al, ,1978Parkinson et al, 1983; Dannan et al, 1983). FireMaster can apparently act as both a genotoxic and epigenetic carcinogen.…”

mentioning

confidence: 99%

Synthesis and identification of highly toxic polybrominated biphenyls in the fire retardant Firemaster BP-6

Robertson¹,

Safe

Parkinson³

et al. 1984

J. Agric. Food Chem.

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“…To determine whether binding of antibodies to a microsomal membrane protein that is not involved in translocation could inhibit translocation, the effect of polyclonal antibodies against a constitutive form of rat liver cytochrome P450 (P450 2c) (Waxman, 1984) was examined using rat liver microsomes. The concentration of this cytochrome in rat liver rough microsomes is at least as high as that of RI ('~1%) (Dannan et al, 1983). Rat liver microsomes had to be used for this experiment since dog pancreas microsomes contain essentially no cytochrome P450 and no antibody against a dog pancreas membrane protein that is not involved in translocation and present in sufficiently high concentration is known.…”

Section: Monovalent Fab Fragments That Recognize a Cytoplasmic Segment Of Ri Inhibit Translocationmentioning

confidence: 99%

Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides.

Sabatini

Kreibich

1990

The Journal of Cell Biology

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Abstract. Polyclonal antibodies directed against ribophorins I and II, two membrane glycoproteins characteristic of the rough endoplasmic reticulum, inhibit the cotranslational translocation of a secretory protein growth hormone into the lumen of dog pancreas or rat liver microsomes. As expected, sitespecific antibodies to epitopes located within the cytoplasmic domain of ribophorin I, but not antibodies to epitopes in the luminal domain of this protein, were effective in inhibiting translocation. Since monovalent Fab fragments were as inhibitory as intact IgG molecules, ribophorins must be closely associated with the translocation site and, therefore, are likely to function at some stage in the translocation process. In all cases, the antibodies that inhibited translocation also caused a significant reduction in total protein synthesis and treatments that neutralized their capacity to inhibit translocation also prevented their inhibitory effect on protein synthesis. This would be expected if the antibodies blocked the membrane-mediated relief of the SRP-induced arrest of polypeptide elongation. The antibodies were effective only when added before translocation was allowed to begin. In this case, they prevented the targeting of active ribosomes containing mRNA and nascent chains to the ER membrane. Thus, ribophorins must either directly participate in targeting or be so close to the targeting site that the antibodies sterically blocked this early phase of the translocation process.

show abstract

Regulation of cytochrome P-450. Immunochemical quantitation of eight isozymes in liver microsomes of rats treated with polybrominated biphenyl congeners.

Cited by 131 publications

References 35 publications

Interaction of Polycyclic Aromatic Hydrocarbons and Flavones with Cytochromes P450 in the Endoplasmic Reticulum: Effect on CO Binding Kinetics

Interaction of Polycyclic Aromatic Hydrocarbons and Flavones with Cytochromes P450 in the Endoplasmic Reticulum: Effect on CO Binding Kinetics

Synthesis and identification of highly toxic polybrominated biphenyls in the fire retardant Firemaster BP-6

Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides.

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