Suppression of hepatic ribonuclease during phenobarbital stimulation of drug metabolism

Louis-Ferdinand, Robert T.; Fuller, George C.

doi:10.1016/0006-291x(70)90654-6

Cited by 37 publications

(6 citation statements)

References 8 publications

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“…These enzymes are not known to be induced in adult chickens by the drug . The specific activity of ribonuclease (Louis-Ferdinand and Fuller, 1970) in chick embryo liver is maintained in organ culture, but falls 50% in the presence of 5 .5 mm phenobarbital, supporting observations made in vivo (Seifert and Remmer, 1971) . CHANGE IN CULTURE CONDITIONS : Monolayer cell cultures were prepared from 11-day embryo liver by the method of Skea and Nemeth (1969) .…”

Section: Relation Of Enzyme Development To Protein and Rna Synthesissupporting

confidence: 75%

Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Burchell

Dutton

Nemeth

1972

The Journal of Cell Biology

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Uridine diphosphate (UDP) glucuronyltransferase activity in chick liver rises at hatching from near zero to adult levels. This rise will occur prematurely in embryo liver during organ culture. Increase in enzyme activity during organ culture differs with embryo age: in liver from 11-day old embryos it ceases at adult values; in liver from 5-day old embryos it continues to much higher-than-adult levels. Phenobarbital added to culture medium accelerates these rises in enzyme activity and elevates the plateau reached in 11-day embryo liver to that observed in 5-day embryo liver. Kinetic analysis of the changes in enzyme activity induced by phenobarbital during culture suggests that the regulatory mechanisms for enzyme activity are different in 5- and 11-day embryo liver and that these differences reflect developmental changes occurring in ovo.

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Section: Relation Of Enzyme Development To Protein and Rna Synthesissupporting

confidence: 75%

Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Burchell

Dutton

Nemeth

1972

The Journal of Cell Biology

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“…Ribosomes. In most of these experiments adult male rats were given 25 mg of phenobarbital/day, in the drinking water, for 7 days before sacrifice, to reduce the amount of RNase in the liver (Louis-Ferdinand and Fuller, 1970). Liver ribosomes were isolated as described by Petermann and Pavlovec (1963), with some modifications.…”

Section: Methodsmentioning

confidence: 99%

Dissociation of rat liver ribosomes to active subunits by urea

Petermann¹,

Pavlovec²

1971

Biochemistry

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Since ribosomal subunits are sensitive to degradative enzymes, adult male rats were treated with phenobarbital to decrease the liver RNase content. The ribosomes were isolated, dissociated, and reassociated in the presence of 1 mM dithiothreitol. When their bound magnesium was reduced to 0.3 equiv/mole of RNA phosphate, and they were then treated with urea, they dissociated to subunits. The urea was removed by dialysis against a low-magnesium buffer, and the subunits were fractionated in a zonal rotor. With 2 m urea about 50% of the small subunits was recovered in a 40S fraction, 5 % was found in a 28S form, and the rest had dimer-T A he ribosomes of Escherichia coli can readily be dissociated to 30S and 50S subunits by a moderate reduction in their bound magnesium. When the magnesium is restored to its initial level these subunits reassociate to 70S ribosomes that are active in protein synthesis (Staehelin and Meselson, 1966). Mammalian 80S ribosomes, on the other hand, do not usually dissociate until their bound magnesium has been reduced to a very low level, and this type of dissociation frequently results in unfolding of the subunits, detachment of the 5S RNA, and irreversible loss of activity (Petermann et al., 1969). Active subunits can be obtained from animal ribosomes by a highsalt treatment (Martin and Wool, 1969), but since a high-salt wash may remove important factors (Heywood, 1970;Arnstein, 1970) a low-salt procedure may sometimes be preferable. Such a procedure is described in the present paper. Rat liver ribosomes were dissociated to active subunits by removing half their bound magnesium and adding urea. The 5S RNA was not detached, and the subunits remained in compact forms that could reassociate to 81S particles that were active in protein synthesis. MethodsRibosomes. In most of these experiments adult male rats were given 25 mg of phenobarbital/day, in the drinking water, for 7 days before sacrifice, to reduce the amount of RNase in the liver (Louis-Ferdinand and Fuller, 1970). Liver ribosomes were isolated as described by Petermann and Pavlovec (1963), with some modifications. Dithiothreitol (DTT),*

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“…This idea is based upon the fact that RNase activity is elevated under several circumstances in which the RNA/DNA ratio is reduced (3)(4)(5) and conversely, activity of this enzyme decreases under certain conditions in which the RNA/DNA ratio increases (6,7). RNA turnover studies indicate that in these situations the changes in cellular RNA content are due to changes in the rate of RNA catabolism rather than in the rate of RNA synthesis (8,9).…”

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confidence: 99%

Changes in Alkaline Ribonuclease Activity During Compensatory Renal Growth

Rosso

Diggs

Winick

1973

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

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Unilateral nephrectomy in rats produces an increase in ribonuclease activity in both nuclear and cytoplasmic fractions of the contralateral kidney. The timing of this increase and the changes in the proportion of free activity to protein-bound activity are different in each fraction. A peak in inhibitor-bound ribonuclease, suggesting a higher amount of inhibitor, was found in the cytoplasmic fraction before the increase in RNA/DNA ratio. Ninety-six hours after the operation, ribonuclease was still significantly increased in both the nuclear and cytoplasmic fractions. The inhibitor-bound activity was increased in proportion to cellular RNA, maintaining a ribonuclease activity per ,ug of RNA similar to the controls.Alkaline ribonuclease (RNase) activity (pH 7.8) is present in the nucleus and the cytoplasm of most mammalian cells in both the free form and bound to an inhibitor protein. The inhibitor-bound activity may be released in vitro by addition of p-chloromercuribenzoate (PCMB) or other substances that react with -SH groups (1).It has been hypothesized that RNase may regulate the quantity of cytoplasmic RNA by influencing the rate of RNA degradation (2). This idea is based upon the fact that RNase activity is elevated under several circumstances in which the RNA/DNA ratio is reduced (3-5) and conversely, activity of this enzyme decreases under certain conditions in which the RNA/DNA ratio increases (6, 7). RNA turnover studies indicate that in these situations the changes in cellular RNA content are due to changes in the rate of RNA catabolism rather than in the rate of RNA synthesis (8, 9). However, other data do not seem to support such a role for RNase. For example, RNase activity increases in the remaining kidney within 1 hr after uninephrectomy (10), a stimulus that increases the rate of RNA synthesis and elevates the RNA/DNA ratio in the contralateral kidney (11). However, this study measured the activity of only free RNase in whole organ homogenate. Consequently, it is impossible to know whether these changes in RNase activity are occurring in the cytoplasmic or nuclear fraction, where presumably different influences on RNA metabolism are exerted, or if the changes in activity correspond to a de novo synthesis of enzyme or to a decrease in the amount of RNase inhibitor.The present study was undertaken to examine both free and total RNase activity in the nuclear and cytoplasmic fractions of the contralateral kidney after uninephrectomy and to cor- In addition, since changes in the RNA/DNA ratio in shamoperated mice have been reported (11), the effects of sham operation have also been studied. MATERIALS AND METHODSMale Sprague-Dawley rats weighing 300-350 g were fed a standard diet (Purina lab chow) ad libitum and kept on a 12-hr light-dark cycle. Without previous starvation of the rats, a left uninephrectomy or a sham operation was performed under light ether anesthesia. The entire procedure was done within 5 min, and, in the long-term experiments, all animals included in the study had resumed n...

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Suppression of hepatic ribonuclease during phenobarbital stimulation of drug metabolism

Cited by 37 publications

References 8 publications

Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Development of Phenobarbital-Sensitive Control Mechanisms for Uridine Diphosphate Glucuronyltransferase Activity in Chick Embryo Liver

Dissociation of rat liver ribosomes to active subunits by urea

Changes in Alkaline Ribonuclease Activity During Compensatory Renal Growth

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