scholarly journals A model for the regulation of δ-aminolaevulinate synthetase induction in rat liver

1973 ◽  
Vol 134 (4) ◽  
pp. 847-857 ◽  
Author(s):  
Govindarajan Padmanaban ◽  
Manchanahalli R. Satyanarayana Rao ◽  
Krishnamachari Malathi
Keyword(s):  
Rat Liver ◽  
Actinomycin D ◽  
Reciprocal Relationship ◽  
Synthetase Activity ◽  
Drug Resistant ◽  
Adult Rats ◽  
Adult Rat ◽  
Young Rats ◽  
Young Rat ◽  
Cytochrome P 450

A reciprocal relationship exists between the cytochrome P-450 content and δ-aminolaevulinate synthetase activity in adult rats. In young rats the basal δ-aminolaevulinate synthetase activity is higher and the cytochrome P-450 content is lower compared with the adult rat liver. Administration of allylisopropylacetamide neither induces the enzyme nor causes degradation of cytochrome P-450 in the young rat liver, unlike adult rat liver. Allylisopropylacetamide fails to induce δ-aminolaevulinate synthetase in adrenalectomized–ovariectomized animals or intact animals pretreated with successive doses of the drug, in the absence of cortisol. The cortisol-mediated induction of the enzyme is sensitive to actinomycin D. Allylisopropylacetamide administration degrades microsomal haem but not nuclear haem. Haem does not counteract the decrease in cytochrome P-450 content caused by allylisopropylacetamide administration, but there is evidence for the formation of drug-resistant protein-bound haem in liver microsomal material under these conditions. Phenobarbital induces δ-aminolaevulinate synthetase under conditions when there is no breakdown of cytochrome P-450. On the basis of these results and those already published, a model is proposed for the regulation of δ-aminolaevulinate synthetase induction in rat liver.

scholarly journals The effect of exogenous δ-aminolaevulinate on rat liver haem and cytochromes

1972 ◽  
Vol 129 (5) ◽  
pp. 1095-1099 ◽  
Author(s):  
Robert Druyan ◽  
Aldon Kelly
Keyword(s):  
Rat Liver ◽  
Synthetase Activity ◽  
Adult Rats ◽  
Adult Rat ◽  
Haem Biosynthesis ◽  
Rate Limiting ◽  
Mitochondrial Cytochromes ◽  
Hepatic Cytochrome

The activity of δ-aminolaevulinate synthetase is generally regarded as rate-limiting for hepatic haem biosynthesis. It has been suggested that cytochrome synthesis may also be regulated by changes in δ-aminolaevulinate synthetase activity. This hypothesis was studied by injecting product, δ-aminolaevulinate, into adult rats over a 4–240h period. The concentrations of hepatic mitochondrial cytochromes a, b, c and c1 were unchanged by treatment with δ-aminolaevulinate, allylisopropylacetamide or phenobarbital. In control animals, total microsomal haem content equalled the sum of cytochromes b5 plus P-450. After δ-aminolaevulinate administration the total amount of microsomal haem, measured as the pyridine haemochromogen, exceeded these components, indicating the formation of a ‘free’ haem pool. Haem synthesis does not appear rate-limiting for hepatic cytochrome synthesis in the adult rat.

scholarly journals A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from α1 to β subtypes in adrenergic response during primary culture of rat hepatocytes

1996 ◽  
Vol 316 (3) ◽  
pp. 743-749 ◽  
Author(s):  
Yasuo KAJIYAMA ◽  
Yutaka SANAI ◽  
Michio UI
Keyword(s):  
Primary Culture ◽  
Rat Liver ◽  
Plasma Membranes ◽  
Rat Hepatocytes ◽  
Prior Treatment ◽  
Adult Rats ◽  
Adult Rat ◽  
Liver Membranes ◽  
Young Rat

Adrenergic responses of rat hepatocytes were studied by measuring Ins(1,4,5)P3 (for the response via α1-subtype receptors) and cAMP (for β-subtype response) generation during brief incubation of cells with respective agonists. Hepatocytes from young rats with an age of 1 week displayed a very high β response without a significant α1 response. The β response decreased and the α1 response increased progressively as the age increased; the response was almost exclusively via α1 receptors in hepatocytes of adult rats 9 weeks or more old. The β response developed, again at the expense of the α1 response, in hepatocytes from adult rats during the primary culture at low cell densities [(1–2.5)×104 cells/cm2]. Such ‘α1 to β subtype switching’ of adrenergic responses in vitro was totally inhibited by adding plasma membranes prepared from adult rat liver into the low-cell-density culture, but not inhibited at all by membranes from young rat liver. The inhibitory effect of adult rat liver membranes was lost when the membranes had been exposed to endoglycosidase F or β-galactosidase but was not affected by prior treatment with sialidase. On the contrary, young rat liver membranes became inhibitory to ‘α1 to β subtype switching’ after prior treatment with sialidase. Thus glycoproteins with unsialylated galactosyl termini on the surface of adult rat hepatocytes are likely to function as a determinant of the relative development of α1/β subtypes of adrenergic responses; the β response is predominant in hepatocytes in the juvenile, presumably as a result of sialylation of the galactosyl termini of the functional glycoproteins.

Comparison of cytochrome P-450 levels in adult rat liver, postnatal rat liver, and primary cultures of postnatal rat hepatocytes

Life Sciences ◽  
1979 ◽  
Vol 25 (16) ◽  
pp. 1413-1418 ◽  
Author(s):  
Daniel Acosta ◽  
David C. Anuforo ◽  
Reagan McMillin ◽  
William H. Soine ◽  
Robert V. Smith
Keyword(s):  
Rat Liver ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Adult Rat ◽  
Cytochrome P 450

Postnatal expression of the canalicular bile acid transport system of rat liver

1991 ◽  
Vol 260 (5) ◽  
pp. G743-G751 ◽  
Author(s):  
D. A. Novak ◽  
C. J. Sippel ◽  
M. Ananthanarayanan ◽  
F. J. Suchy
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Initial Rate ◽  
Kinetic Studies ◽  
Precipitation Method ◽  
Disulfonic Acid ◽  
Acid Transport ◽  
Adult Rats ◽  
Bile Acid Transport ◽  
Adult Rat

Canalicular plasma membrane (CPM) vesicles prepared by a Ca2+ precipitation method from developing (7 and 14 days old) and adult rat liver were used to directly examine the postnatal ontogenesis of taurocholate (TC) transport. The initial rate of 50 microM TC uptake by vesicles derived from 14-day-old and adult but not 7-day-old animals was markedly inhibited by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). DIDS-sensitive TC uptake was 21.6 +/- 5.6 (SE) at 14 days compared with 58.1 +/- 8.1 pmol.mg protein-1.5 s-1 in adults (P less than or equal to 0.01). Kinetic studies were performed by preloading these predominantly "right-side out" vesicles with TC (25-800 microM) and measuring the initial rate (5 s) of efflux into bile salt-free medium. Computer analysis of the DIDS-sensitive portion of efflux revealed saturable kinetics with a similar Vmax (2.72 +/- 0.36 vs. 1.97 +/- 0.17 nmol.mg protein-1.min-1; P = NS) but a threefold higher Km (0.35 +/- 0.09 vs. 0.11 +/- 0.02 mM; P less than or equal to 0.05) in 14 day vs. adult CPM vesicles. In contrast, efflux from 7 day CPM vesicles increased linearly with increasing concentrations of TC and was not inhibited by DIDS. Immunoblots of canalicular membranes, probed with an antibody against the 100-kDa bile acid transport protein, showed that the amount of immunoreactive carrier protein in the membranes of 14-day-old and adult rats was similar but was only 37% of the adult level at 7 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PTH increases renal 25(OH)D3-1α-hydroxylase (CYP1α) mRNA but not renal 1,25(OH)2D3production in adult rats

2003 ◽  
Vol 284 (5) ◽  
pp. F1032-F1036 ◽  
Author(s):  
H. J. Armbrecht ◽  
M. A. Boltz ◽  
T. L. Hodam
Keyword(s):  
Ribonuclease Protection Assay ◽  
Mrna Levels ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Dihydroxyvitamin D ◽  
Fischer 344 ◽  
Young Rats ◽  
Ribonuclease Protection ◽  
Cytochrome P 450

The capacity of parathyroid hormone (PTH) to stimulate renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production declines with age in the rat. The purpose of these studies was to determine whether this decline is due to a decreased capacity of PTH to increase the mRNA levels of CYP1α, the cytochrome P-450 component of the 25(OH)D3-1α-hydroxylase. Young (2 mo) and adult (12 mo) male Fischer 344 rats were parathyroidectomized (PTX). After 72 h, PTX rats were injected with PTH or vehicle at 24, 6, and 3 h before death, and renal CYP1α mRNA levels were measured by ribonuclease protection assay. In young rats, PTH markedly increased plasma 1,25(OH)2D3 and renal 1,25(OH)2D3 production. However, in adult rats, the response to PTH was less than 30% of that seen in young rats. Renal CYP1α mRNA levels, on the other hand, were increased over fivefold by PTH in both young and adult rats. In in vitro studies, PTH/forskolin increased CYP1α mRNA levels over twofold in renal slices from both young and adult PTX rats. These studies demonstrate that the decreased capacity of PTH to increase 1,25(OH)2D3 production in adult rats is not due to decreased induction of CYP1α mRNA.

scholarly journals Immunocytochemical staining of the RLM6 form of cytochrome P-450 in oligodendrocytes and myelin of rat brain.

1991 ◽  
Vol 39 (8) ◽  
pp. 1089-1094 ◽  
Author(s):  
W Cammer ◽  
M Downing ◽  
W Clarke ◽  
J B Schenkman
Keyword(s):  
Rat Brain ◽  
Ketone Bodies ◽  
Immunofluorescence Staining ◽  
Immunocytochemical Staining ◽  
Double Immunofluorescence ◽  
Adult Rats ◽  
Adult Rat ◽  
Myelinated Fibers ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Cytochrome P 450

We used immunocytochemical staining to localize the RLM6 form of cytochrome P-450 in rat brain. Immunofluorescence staining in vibratome sections was positive in cells that resembled oligodendrocytes, which are the cells that synthesize and maintain myelin. Double immunofluorescence staining with anti-RLM6, plus mouse monoclonal antibodies (MAb) against 2',3'-cyclic nucleotide-3'-phosphohydrolase or galactocerebrosides, showed localization of each of these oligodendrocyte "markers" in the same cells as RLM6. In vibratome sections from brains of adult rats there was faint RLM6 immunostaining in some of the myelinated fibers as well as in oligodendrocytes. In paraffin sections from adult rat brains, myelinated tracts were RLM6 positive, as were oligodendrocytes and myelinated fibers in the gray matter. Oligodendrocytes were also shown to contain glucose-6-phosphate dehydrogenase. We suggest that RLM6, which is constitutive to liver, is also constitutive to brain and, via the acetone monooxygenase reaction, which also utilizes NADPH, may contribute to the conversion of ketone bodies to substrates that could provide energy for the synthesis and maintenance of myelin.

Hepatic stimulator substance: physicochemical characteristics and specificity

1982 ◽  
Vol 242 (3) ◽  
pp. G281-G288 ◽  
Author(s):  
D. R. LaBrecque ◽  
N. R. Bachur
Keyword(s):  
Rat Liver ◽  
Nuclear Dna ◽  
Tritiated Thymidine ◽  
Fold Increase ◽  
Physicochemical Characteristics ◽  
Adult Rats ◽  
Hepatic Stimulator Substance ◽  
Adult Rat ◽  
Heat Stable ◽  
Organ Specific

This laboratory has reported previously that a cytoplasmic extract of weanling or regenerating adult rat liver (but not normal rat liver) will produce a 2.5-fold increase in the incorporation of tritiated thymidine ([3H]dThd) into liver DNA of a 34%-hepatectomized test animal. (J. Physiol. London 248: 273-284, 1975). The present study showed that hepatic stimulator substance (HSS) will stimulate DNA synthesis in normal adult rats and CF1 mice as well. The increased incorporation of [3H]dThd into DNA produced in the normal, nonhepatectomized adult rat was comparable with that induced by a 34% hepatectomy. Autoradiographic studies revealed that the [3H]dThd was incorporated into nuclear DNA and that the stimulation occurred almost exclusively in parenchymal cells. HSS was shown to be heat stable (100 degrees C for 15 min) and was precipitated but not inactivated by alcohol. Ultrafiltration and dialysis studies suggested a molecular weight slightly greater than 10,000. HSS proved to be organ specific, stimulating the liver but not the kidney, bone marrow, or spleen. HSS was found to contain no insulin, glucagon, epidermal growth factor, or peptides of the nonsuppressible insulinlike/multiplication-stimulating activity (somatomedin) group.

Cholestasis is associated with preproenkephalin mRNA expression in the adult rat liver

1995 ◽  
Vol 268 (2) ◽  
pp. G346-G354 ◽  
Author(s):  
N. V. Bergasa ◽  
S. L. Sabol ◽  
W. S. Young ◽  
D. E. Kleiner ◽  
E. A. Jones
Keyword(s):  
Rat Liver ◽  
Northern Blotting ◽  
Cholestatic Liver Disease ◽  
Elevated Plasma ◽  
Bile Duct Resection ◽  
Adult Rats ◽  
Adult Rat ◽  
Hepatocellular Necrosis ◽  
Low Levels ◽  
Experimental Findings

Cholestatic liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total opioid activity, and elevated plasma enkephalin concentrations. In contrast to the normal adult rat liver, preproenkephalin mRNA was detected by Northern blotting in livers of adult rats with cholestasis due to bile duct resection and not in the sham-resected controls. Preprodynorphin mRNA was not detected in livers of either group, while preproopiomelanocortin mRNA was found in very low levels in both groups. Preproenkephalin mRNA was not expressed in the livers of rats with acute hepatocellular necrosis induced by thioacetamide. Hybridization histochemistry of cholestatic livers demonstrated the presence of preproenkephalin mRNA primarily over cells in the periportal areas, some of which appeared to be proliferating bile ductular cells. Immunohistochemical staining of cholestatic liver indicated the production of at least Met-enkephalin in association with preproenkephalin gene expression. These findings suggest that the liver itself, by synthesizing enkephalins, contributes directly to the abnormalities of the opioid system reported in cholestasis.

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