In Vivo Interactions of Aluminum with Hepatic Cytochrome P-450 and Metallothionein

1987 ◽  
Vol 8 (4) ◽  
pp. 541-548
Author(s):  
E. H. JEFFERY ◽  
H. T. JANSEN ◽  
J. A. DELLINGER
Keyword(s):  
Cytochrome P 450 ◽  
Hepatic Cytochrome

scholarly journals Olfactory cytochrome P-450. Studies with suicide substrates of the haemoprotein

1988 ◽  
Vol 253 (2) ◽  
pp. 569-576 ◽  
Author(s):  
C J Reed ◽  
E A Lock ◽  
F De Matteis
Keyword(s):  
Olfactory Epithelium ◽  
Peroxidase Activity ◽  
Time Course ◽  
Cumene Hydroperoxide ◽  
Enzymic Activity ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome ◽  
Suicide Substrates

1. The olfactory epithelium of male hamsters has been found to be extremely active in the cumene hydroperoxide-supported oxidation of tetramethylphenylenediamine, and this peroxidase activity has been shown to be cytochrome P-450-dependent. 2. The interaction of a series of suicide substrates of cytochrome P-450 with the hepatic and olfactory mono-oxygenase systems has been assessed by determination of peroxidase, 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) activities after treatment in vivo with these compounds. Chloramphenicol, OOS-trimethylphosphorothiolate and two dihydropyridines [DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and 4-ethyl DDC (3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine)] all caused similar percentage inhibitions of hepatic and olfactory activities, but the absolute amounts of enzymic activity lost were considerably greater in the latter tissue. In contrast, halothane had little effect upon hepatic cytochrome P-450-dependent reactions, whereas it severely inhibited those of the olfactory epithelium. 3. The time course of loss and recovery of hepatic and olfactory peroxidase, ECOD and EROD activities after a single dose of 4-ethyl DDC was studied. The rates of loss of activity observed were very similar, irrespective of tissue or reaction examined. In the olfactory epithelium, all three activities recovered concurrently and at a rate similar to that of the hepatic peroxidase activity. In contrast, the hepatic de-ethylation of 7-ethoxycoumarin and 7-ethoxy-resorufin recovered significantly more rapidly. 4. It is suggested that this behaviour is due to 4-ethyl DDC acting not only as a suicidal inhibitor but also as an inducer of certain forms of cytochrome P-450 in the liver; in the olfactory epithelium, however, inactivation, but not induction, occurs. Classical inducing agents were reported to have no effect upon olfactory cytochrome P-450, and in the present study neither phenobarbitone nor beta-naphthoflavone treatment had any effect upon olfactory cytochrome P-450-dependent reactions, although it induced those of the liver.

EXOGENOUS HEME FUNCTIONALLY RECONSTITUTES HEPATIC CYTOCHROME P-450 IN VIVO

1980 ◽  
pp. 587-590 ◽  
Author(s):  
Geoffrey C. Farrell ◽  
M. Almira Correia ◽  
Rudi Schmid ◽  
Paul R. Ortiz de Montellano ◽  
Kent L. Kunze
Keyword(s):  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Exogenous heme restores in vivo functional capacity of hepatic cytochrome P-450 destroyed by allylisopropylacetamide

1979 ◽  
Vol 89 (2) ◽  
pp. 456-463 ◽  
Author(s):  
Geoffrey C. Farrell ◽  
Rudi Schmid ◽  
Kent L. Kunze ◽  
Paul R. Ortiz de Montellano
Keyword(s):  
Functional Capacity ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

scholarly journals Incorporation of exogenous heme into hepatic cytochrome P-450 in vivo.

1979 ◽  
Vol 254 (1) ◽  
pp. 15-17
Author(s):  
M.A. Correia ◽  
G.C. Farrell ◽  
R. Schmid ◽  
P.R. Ortiz de Montellano ◽  
G.S. Yost ◽  
...  
Keyword(s):  
Cytochrome P 450 ◽  
Hepatic Cytochrome

scholarly journals Immunochemical quantification of cytochrome P450IA and IIB subfamilies in the livers of metyrapone-treated rats. Relevance to the ability of metyrapone to prevent the loss of cytochrome P-450 in rat hepatocyte culture

1990 ◽  
Vol 267 (3) ◽  
pp. 715-719 ◽  
Author(s):  
K Shean ◽  
A J Paine
Keyword(s):  
Polyclonal Antibodies ◽  
Rat Hepatocytes ◽  
Microsomal Protein ◽  
Hepatocyte Culture ◽  
Rat Hepatocyte ◽  
Rat Hepatocyte Culture ◽  
Rat Livers ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome

Polyclonal antibodies to the major beta-naphthoflavone (BNF)-inducible form of cytochrome P-450 (P450IA) and to the major phenobarbitone (PB)-inducible form (P450IIB) have been used to quantify the contribution of these subfamilies to the total amount of cytochrome P-450 in rat livers and rat hepatocyte cultures treated with PB, BNF and metyrapone for 24 and 72 h. The P450IA and IIB subfamilies were not detectable (less than 5 pmol/mg of microsomal protein) in the livers of control rats, but administration of BNF resulted in the P450IA subfamily comprising more than 80% of the total hepatic cytochrome P-450. Administration of PB and metyrapone to rats did not elevate the level of this subfamily but elevated the levels of the P450IIB subfamily to 60% and 30% respectively of the total. Thus metyrapone is a ‘PB-like’ inducer. However, in contrast with their effects in vivo, treatment with PB and metyrapone of rat hepatocytes did not elevate the proportion of the P450IIB subfamily relative to that in untreated cells but rather, like BNF, increased the P450IA subfamily. This would account for the ability of metyrapone to produce in hepatocyte culture, like BNF, a pronounced induction of ethoxyresorufin O-de-ethylase activity, but it does not account for why of all inducers studied only metyrapone can maintain the total cytochrome P-450 content of cultured hepatocytes, or the activity of ethylmorphine N-demethylase. This activity is generally considered to be associated with the P450IIB subfamily, but the lack of effect of metyrapone on this subfamily in hepatocyte culture must suggest that metyrapone is able to prevent the loss of the total amount of the cytochrome by increasing the expression of other cytochromes P-450.

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