Microsomal Cytochromes in the Immature and Adult Rat Brain

Holtzman, David; Desautel, Marcia

doi:10.1111/j.1471-4159.1980.tb11237.x

Cited by 17 publications

(5 citation statements)

References 8 publications

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“…The concentration of mung-bean cytochrome P-450, at its optimum of 0.066 nmol/mg of microsomal protein (day 4), is similar to that of germinating pea cotyledons and cauliflower buds (Rich & Bendall, 1975). In mammals cytochrome P-450 concentrations typically range from about 0.03nmol/mg of protein in rat brain (Holtzman & Desautel, 1980) to over 1.0nmol/mg of protein in rat liver (Matsubara et al, 1976) or more in other species (Omura & Sato, 1964). Cytochrome P-420 concentrations in mung beans and other plant species (Rich & Bendall, 1975) appear to be considerably higher than in mammals.…”

Section: Discussionmentioning

confidence: 80%

“…In contrast, cytochrome b5/cytochrome P-450 ratios in mammals are usually in the region of 1: 1 to 1 :2 (rabbit and rat liver microsomal fractions) (Omura & Sato, 1964;Matsubara et al, 1976). Only in rat brain microsomal fractions are high cytochrome b5/cytochrome P-450 ratios (about 3: 1) reported (Holtzman & Desautel, 1980). Oshino (1978) considered that cytochromes b5 and P-450 occur together in 'mixed-function oxidase' complexes in most mammalian organs, with the exception of brain tissue, where he considered that the excess of cytochrome b5 over cytochrome P-450 indicated that cytochrome b5 may exist as an independent reductase.…”

Section: Discussionmentioning

confidence: 99%

“…The functions of cytochromes P-450 and b5 in plant microsomal fractions appear to correspond to certain of those in mammalian systems (e.g. hydroxylation of lipid-soluble compounds), though the overall role of cytochrome b5 remains elusive both in mammals (Oshino, 1978;Holtzman & Desautel, 1980) and in plants (Rich & Lamb, 1977). However, our evidence suggests that there exists, in plants, a short-lived requirement for cytochrome P-450-mediated reactions that may become largely redundant as the seedling achieves photosynthetic competence or, in etiolated tissue, approaches premature senescence.…”

Section: Discussionmentioning

confidence: 99%

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The cytochromes in microsomal fractions of germinating mung beans

Hendry¹,

Houghton²,

Jones³

1981

Biochemical Journal

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Detailed studies of microsomal cytochromes from mung-bean radicles showed the presence of cytochrome P-420, particularly in dark-grown seedlings, accompanied by smaller quantities of cytochrome P-450. Similar proportions of cytochrome P-420 to cytochrome P-450 were found spectrophotometrically in vivo with whole radicles and hypocotyls. Assayed in vitro, maximum concentrations of both cytochromes were attained after 4 days of growth, before undergoing rapid degradation. Illumination of seedlings stabilized cytochrome P-450 and decreased the amount of cytochrome P-420. Three b cytochromes were present in the microsomal fraction, namely cytochromes b-562.5 (Em + 105 +/- 23 mV), b-560.5 (Em + 49 +/- 13 mV) and b5 (Em - 45 +/- 14 mV), all at pH 7.0. Of the b cytochromes, cytochrome b5 alone undergoes a rapid degradation after day 4, Changes in cytochrome b concentrations were confined to the microsomal fraction: mitochondrial b cytochrome concentrations were unaltered with age. Protohaem degradation (of exogenous methaemalbumin) was detected in microsomal fractions of mung beans. The rates of degradation were highest in extracts of young tissue and declined after day 4. The degradation mechanism and products did not resemble those of mammalian haem oxygenase.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The cytochromes in microsomal fractions of germinating mung beans

Hendry¹,

Houghton²,

Jones³

1981

Biochemical Journal

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“…The level of P450 in the brain microsomes, quantitated by its carbon monoxide difference spectrum, has been estimated in several laboratories to be 1-3% of that in the liver (15)(16)(17)(18). We have found it impossible to measure P450 in brain microsomal fractions, but after extraction by hydrophobic chromatography, the enzyme can be quantitated spectrally.…”

mentioning

confidence: 96%

Effect of ethanol on cytochrome P450 in the rat brain.

Warner

Gustafsson

1994

Proc. Natl. Acad. Sci. U.S.A.

110

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After a single dose of ethanol (0.8 ml/kg) administered intraperitoneally, the P450 content of the rat brain increased from 62 + 19 to 230 ± 97 pmol/g (wet weight) of tissue (mean ± SD, n = 5). Most of this increase could be accounted for by a 10-to 20-fold increase in the olfactory lobes and hypothalamic preoptic area. The P450s were identified by Western blot analysis and by microsequencing of the N-terminal ends after resolution of the proteins on SDS gels. They were identified as P450 2C7, 2C11, 2E1, 4A3, 4A8, and a member of the P450 2D family. In P450 extracted from the brains of control rats, P450 2C and 4A were also detectable but at a much lower concentration. P450 lA1, 2A1, 2B1, or 3A was not detected in the brains of either control or ethanol-treated rats. Oral administration of the same dose of ethanol resulted in a similar increase in the whole brain but smaller effects in the olfactory lobes. This effect of ethanol on the P450 in the brain has implications for the mechanism of toxicity and the development of tolerance to ethanol and for the effects of other drugs and environmental pollutants that act on the central nervous system.The mechanisms responsible for the intoxication, dependence, and neurotoxicity of ethanol remain largely unknown, and current data on the subject have been extensively reviewed (1-4). Of the many biochemical changes that occur in the body upon ingestion of ethanol, the induction of cytochrome P450 2E1 in the liver (5) has received much attention, not only because of the capacity of this isozyme to metabolize ethanol to acetaldehyde but also because of the potential of this enzyme to cause cellular damage. P450 2E1 can metabolically activate xenobiotics such as halothane and carbon tetrachloride to cytotoxins and nitrosamines to carcinogens (for review, see ref. 6). In addition there is a high production of oxygen radicals during its catalytic cycle, and this leads to lipid peroxidation and destruction of cell membranes (7). P450 2E1 is constitutive in the rat liver and the level ofthe protein, but not its mRNA, is increased by ethanol (8).-The enzyme is also detectable in the kidney and lung at levels that are <10% of that in the liver (9). The presence of P450 2E1 in the brain and its inducibility by ethanol is controversial. Immunohistochemical evidence indicates the presence of P450 2E1 in the brains of untreated rats in some studies (10, 11) but not in others (12), and chronic exposure of rats to ethanol in drinking water was found in one study (12) to increase the level of P450 2E1 in the brain. In the human cDNA libraries, the cDNA of P450 2E1 has been detected (13) but it is not known whether this is constitutive or due to exposure to ethanol or any of the many other organic solvents that induce this enzyme (14).The level of P450 in the brain microsomes, quantitated by its carbon monoxide difference spectrum, has been estimated in several laboratories to be 1-3% of that in the liver (15-18). We have found it impossible to measure P450 in brain microsomal fra...

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“…The level of P-450 in the brain is estimated to be 3-35 pmol/mg of microsomal protein (Marietta et al, 1979;Holtzman and Desautel, 1980;Nabeshima et al, 1984;Qato and Maines, 1985;Walther et a]., 1986), which is 0.3-3% of the level in liver microsomes. Very little is known about the regional distri-bution of different forms of P-450 in the brain.…”

mentioning

confidence: 99%

Regional Distribution of Cytochrome P‐450 in the Rat Brain: Spectral Quantitation and Contribution of P‐450b,e and P‐450c,d

Warner

Køhler²,

Hansson

et al. 1988

Journal of Neurochemistry

142

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The cytochrome P-450 (P-450) content of different regions of the rat brain was measured after partial purification of the enzyme from homogenates, and the quantitative contribution of P-450b,e and P-450c,d to brain P-450 was assessed by Western immunoblotting and immunohistochemistry using rabbit antibodies raised against purified hepatic P-450b and P-450c, respectively). P-450 could be quantitated by its reduced CO difference spectrum after chromatography of homogenates on p-chloroamphetamine-coupled Sepharose. The yield of P-450 from whole brain was 90 +/- 19 pmol/g of tissue, which is approximately 1% of the level in liver microsomes from control rats. The amount of P-450 recovered from homogenates of olfactory lobes, hypothalamus, thalamus, striatum, cerebral cortex, and brainstem varied between 40 and 100 pmol/g of tissue. The cerebellum was a region of exceptionally high P-450 content, with yields of up to 400 pmol/g whereas the substantia nigra yielded only 16-20 pmol/g. Immunohistochemical studies with anti-P-450b and anti-P-450c revealed intense staining of a limited number of cells in the cerebellum with both antibodies and in the thalamus only with anti-P-450c. In the cerebellum, both anti-P-450b and anti-P-450c stained the Bergmann glial cells together with their radial processes. Individual glial cells in the granular cell layer were also stained. There was no staining of Purkinje cells. In the thalamus, anti-P-450b gave weak staining of certain astroglia, but with anti-P-450c, there was intense staining of neuronal somata.(ABSTRACT TRUNCATED AT 250 WORDS)

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Microsomal Cytochromes in the Immature and Adult Rat Brain

Cited by 17 publications

References 8 publications

The cytochromes in microsomal fractions of germinating mung beans

The cytochromes in microsomal fractions of germinating mung beans

Effect of ethanol on cytochrome P450 in the rat brain.

Regional Distribution of Cytochrome P‐450 in the Rat Brain: Spectral Quantitation and Contribution of P‐450b,e and P‐450c,d

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