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F Possmayer

Publications and source records attributed to F Possmayer.

At least 145 records · Page 8Linked to original sources
PubMed1979

Glucocorticoid induction of pulmonary maturation in the rabbit fetus. The effect of maternal injection of betamethasone on the activity of enzymes in fetal lung.

1. Maternal administration of betamethasone (0.2 mg/kg) on day 25 or 26 of gestation produced a significant decrease in the lung/body weight ratio of the rabbit fetuses within 24 h. 2. The incorporation of [14C]choline but not [14C]ethanolamine into the lipids of fetal lung slices was significantly increased, indicating that there was a specific effect on phosphatidylcholine synthesis. 3. The activities of a number of marker enzymes for subcellular organelles were elevated, especially in the lungs of fetuses delivered on day 26. The increases in monoamine oxidase (mitochondrial outer membrane), beta-glycerophosphatase and aqueously dispersed phosphatidic acid-dependent phosphatidic acid phosphohydrolase (lysosomal) activities were significant. 4. Although the activity of cholinephosphotransferase was not affected by glucocorticoid treatment, the activities of glycerol-3-phosphate phosphatidyltransferase and the activities of two enzymes in the auxiliary pathways for the production of disaturated phosphatidylcholine (lysophosphatidylcholine:lysophosphatidylcholine transacylase and lysophosphatidylcholine:acyl-CoA acyl-transferase) were significantly increased. 5. Membrane-bound phosphatidic acid-dependent phosphatidic acid phosphohydrolase activity was elevated to a lesser extent than the aqueously dispersed phosphatidate-dependent activity and this increase was not significant. 6. The incorporation of E135S]methionine into protein by slices of fetal lung was significantly reduced after maternal treatment with betamethosone. 7. These results are consistent with the general view that glucocorticoids can induce pulmonary maturation and surfactant production in the rabbit fetus but indicate that some of the former hypotheses regarding the mechanism by which lipid synthesis is accelerated must be reevaluated.

Animals↗
PubMed1979

Pulmonary phosphatidic acid phosphatase. Properties of membrane-bound phosphatidate-dependent phosphatidic acid phosphatase in rat lung.

1. The membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activity of rat lung has been investigated in cytosol and microsomal fractions using as a substrate [32P]phosphatidate bound to heat inactivated rat liver microsomes. Both activities demonstrated broad pH optima with a maximum of 7.4--8 for the cytosol and a maximum of 6.5--7.5 with microsomal preparations. 2. At low concentrations (0--5 mM) Mg2+ produced a slight stimulation of the cytosol activity but at higher concentrations an inhibition was observed. Low concentrations (1.0--2.0 mM) of EDTA abolished the cytosol activity and reduced the microsomal activity to half. In both cases, the addition of Mg2+ in the presence of EDTA resulted in an activity which was more than 2-fold greater than that observed in the absence of chelator or divalent cation. 3. The cytosol activity was relatively resistant to the addition of ionic and nonionic detergents. In general, the addition of a number of phosphate esters increased rather than decreased the release of 32Pi, indicating a relative specificity for phosphate groups associated with a hydrophobic environment. The addition of aqueous dispersions of phosphatidate, lysophosphatidic acid or phosphatidylglycerophosphate markedly reduced the hydrolysis of membrane-bound [32P]phosphatidate. The cytosol activity was slightly inhibited by the addition of phosphatidylcholine. 4. In an attempt to estimate the relative contributions of the cytosol and microsomal activities in vivo, these activities were assayed using [32P]phosphatidate endogenously generated on rat lung microsomes. With the 32P-labelled microsomes, the hydrolysis remained linear over the 45 min of the experiment. Addition of high speed supernatant produced a rapid release of 32Pi during the first 10 min followed by a more gradual release similar to that oberved with the microsomes alone. The cytosol activity remained greater than the microsomal activity at all times studied. 5. When [14C]phosphatidate-labelled microsomes were incubated in the presence of nonradioactive CDPcholine, the addition of cytosol markedly stimulated the incorporation of radioactivity into phosphatidylcholine. This observation suggests that the phosphatidic acid phosphatase activity associated with the cytosol has a role in phosphatidylcholine (and presumably surfactant) biosynthesis in rat lung.

Animals↗
PubMed1979

Pulmonary phosphatidic acid phosphatase. A comparative study of the aqueously dispersed phosphatidate-dependent and membrane-bound phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung.

1. The properties of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase (EC 3.1.3.4) activities of rat lung have been studied in microsomal and cytosol preparations and compared with the properties of the membrane-bound phosphatidate-dependent activities. 2. The microsomal phosphatidic acid phosphatase displayed a prominent pH optimum at 6.5 with a minor peak which varied between 7.5--8 in different experiments. With the cytosol, the major activity was at the higher pH (7.5--8.0) but a distinct optimum was also observed at pH 6.0--6.5. With the membrane-bound substrate, a single broad optimum was observed between pH 7.4 and 8.0 with the cytosol and 6.5--7.5 with the microsomal fraction. 3. Subcellular fractionation studies revealed that the microsomal fraction possessed the greatest proportion of the total phosphatidic acid phosphatase activity and the highest relative specific activity. However, studies with marker enzymes indicated that the aqueously dispersed phosphatidate-dependent activity could be present in plasma membrane, lysosomes and osmiophilic lamellar bodies as well as in the endoplasmic reticulum. 4. The aqueously dispersed phosphatidic acid-dependent activities present in the microsomal and supernatant fractions were inhibited by Ca2+, Mn2+, F- and by high concentrations of Mg2+. In contrast to the membrane-bound phosphatidate-dependent activities, there was little Mg2+ stimulation and only a very slight inhibitory effect was noted with EDTA. A small EDTA-dependent Mg2+ stimulation could be observed with the microsomal fraction but only at the lower pH optimum (6.5). 5. The presence of a number of phosphate esters tended to stimulate rather than inhibit the microsomal activity, indicating that the hydrolase is relatively specific for lipid substrates. Marked inhibitions were noted with lysophosphatidic acid and phosphatidylglycerol phosphate. Phosphatidylcholine produced a slight inhibition. 6. The results indicate that the bulk of the aqueously dispersed phosphatidate-dependent phosphatidic acid phosphatase activities of rat lung microsomes and cytosol is not related to the activities observed with membrane-bound phosphatidate. The Mg2+-dependent hydrolase activities may be synonymous. However, unequivocal conclusions will only be possible when the polypeptide or polypeptides responsible for these activities can be purified.

Animals↗
PubMed1977

Fetal utilization of maternally derived ketone bodies for lipogenesis in the rat.

When D-beta-[3-14C]hydroxybutyrate was injected via the femoral vein into pregnant Sprague-Dawley rats at 21 days of gestation, D-beta-[3-14C]hydroxybutyrate was enzymatically detected in fetal plasma within 5 min. The time course of the incorporation of DL-beta-[3-14C]hydroxybutyrate into fetal lipids was studied. Lipid extracts of brown adipose tissue exhibited the greatest relative incorporation followed by pancreas, liver and lung. Less radioactivity was incorporated into brain and placenta. The incorporation into fetal lipids was several-fold greater than into maternal lipids. The labelling of the individual phospholipids was similar in the different tissues with phosphatidylcholine accounting for more than 50%. 75% of the radioactivity in brown adipose tissue was in the triacylglycerol fraction. In brain, liver and placenta, approximately half of the neutral lipid radioactivity was in cholesterol. Experiments in which D-beta-[3-14C]hydroxybutyrate was directly injected into fetuses in utero confirmed that this substrate was directly used by the fetuses without maternal intervention. These studies demonstrate that the rat placenta is permeable to beta-hydroxybutyrate and suggest that this ketone body is rapidly used by the fetus for the synthesis of fatty acids and cholesterol.

Adipose Tissue, Brown↗
PubMed1977

Cortisol induction of pulmonary maturation in the rabbit foetus. Its effects on enzymes related to phospholipid biosynthesis and on marker enzymes for subcellular organelles.

1. Cortisol treatment of rabbit foetuses in utero at 24 days gestation produced a significant decrease in the lung-weight to body-weight ratio compared with littermate controls by day 26. Histological examination revealed that the alveoli of the treated lungs were more open, the walls were thinner and the osmiophilic bodies were more numerous. 2. Cortisol treatment as described above produced significant increases (P<0.05) in the rates of incorporation of [(14)C]choline into phosphatidylcholine and of [(14)C]ethanolamine into phosphatidylethanolamine in vitro compared with littermate controls. This indicates that glucocorticoids produce an overall increase in phospholipid metabolism rather than a specific increase in phosphatidylcholine production. 3. The addition of 1,2-diacyl-sn-glycerols from egg phosphatidylcholine produced a 10-fold increase in the activity of choline phosphotransferase and a 3-fold increase in the activity of ethanolamine phosphotransferase in rabbit lung homogenates. The addition of 1,2-dipalmitoyl-sn-glycerol did not affect these activities. These results demonstrate that in the presence of exogenous 1,2-dipalmitoyl-sn-glycerol, the activities of these enzymes are dependent on the presence of endogenous 1,2-diacylglycerols. 4. Cortisol administration had no significant effect on the activity of choline phosphotransferase or ethanolamine phosphotransferase with endogenous or exogenously added diacylglycerols. The activities of other endoplasmic-reticulum enzymes (sn-glycerol 3-phosphate phosphatidyltransferase, sn-glycerol 3-phosphate acyltransferase and NADPH-cytochrome c reductase) were not significantly altered by the hormone administration. Oestrone sulphate sulphohydrolase activity was significantly decreased (P<0.05) by cortisol injection, but this effect varied with the foetuses from different does. 5. Cortisol administration had no effect on the activities of mitochondrial (monoamine oxidase, succinate dehydrogenase), plasma-membrane (5'-nucleotidase) or lysosomal (acid phosphatase, N-acetyl-beta-d-glucosaminidase) enzymes. The activity of membrane-associated phosphatidate phosphohydrolase, an enzyme associated with the osmiophilic granules of the type-II alveolar cells, was increased in the lungs of treated foetuses, but the difference was not significant (0.10>P>0.05).

Animals↗
PubMed1977

Dexamethasone treatment of the guinea pig fetus: its effects on the incorporation of 3H-thymidine into deoxyribonucleic acid.

Pregnant guinea pigs of 50 to 53 days' gestation (term 63 days) were anesthetized with ether, and their fetuses were injected intramuscularly with 30 mg of dexamethasone or sterile saline. One week later, the fetuses were injected with 3H-thymidine intramuscularly under direct vision at laparotomy; after one hour, the incorporation of thymidine into deoxyribonucleic acid (DNA was analyzed in various fetal tissues. The relative labeling of DNA was significantly depressed in the cerebral hemispheres, cerebellum, medulla oblongata, and midbrain of the treated fetuses compared to their littermate controls. The relative labeling of the DNA of lungs, kidneys, heart, and adrenals was also significantly reduced. Increasing the dose of dexamethasone produced a progressive inhibition of the incorporation of 3H-thymidine into DNA. A variable recovery from the inhibition became apparent by 14 days following exposure to dexamethasone. The evidence suggests that exposure of the fetus to dexamethasone may exert a potentially deleterious effect on fetal tissues.

Adrenal Glands↗
PubMed1973

Regulation by cytidine nucleotides of the acylation of sn-(14C)glycerol 3-phosphate. Regional and subcellular distribution of the enzymes responsible for phosphatidic acid synthesis de novo in the central nervous system of the rat.

1. The regional and subcellular distribution of the incorporation of sn-[(14)C]glycerol 3-phosphate into rat brain lipids in vitro was investigated and compared with the relative specific activity of various chemical and enzyme markers. The similarity between the subcellular distribution of this incorporation and of NADPH-cytochrome c reductase activity indicated that the synthesis of phosphatidic acid via this route correlated with the presence of endoplasmic reticulum. 2. Experiments in which various amounts of the microsomal fraction were added to fixed amounts of nuclear, myelin, nerve-ending and mitochondrial preparations clearly demonstrated that the endoplasmic-reticulum contamination of these fractions was entirely responsible for the incorporation of sn-[(14)C]glycerol 3-phosphate. 3. The presence of CMP or CTP inhibited the incorporation of sn-[(14)C]glycerol 3-phosphate into the whole homogenate. Similar effects were observed with individual fractions, except for the mitochondria. With the mitochondrial fraction the effect of these cytidine nucleotides varied with the preparation, stimulating in some preparations and inhibiting with other preparations. The presence of CDP-choline stimulated the incorporation into the whole homogenate and to a lesser extent into the subcellular fractions. 4. These results indicate that the various organelles of the central nervous system are more dependent on endoplasmic reticulum for the production of glycerolipids de novo than has previously been appreciated.

Acylation↗