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Biomedical subjects

D L Severson

Publications and source records attributed to D L Severson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Inhibition of the hormone-sensitive lipase in adipose tissue by long-chain fatty acyl coenzyme A.

The effects of free fatty acids and fatty acyl esters of coenzyme A and carnitine on the activity of a hormone-sensitive lipase preparation made from pigeon adipose tissue were determined. Oleic acid (100 microM) resulted in a 40% inhibition of lipase activity. A more potent inhibition of lipase activity was seen with long-chain fatty acyl CoA compounds. The concentration required for half-maximal inhibition with oleoyl CoA and palmitoyl CoA was 25-40 microM, whereas palmitoyl carnitine stimulated lipase activity. Activated lipase preparations (preincubated with Mg2+, ATP, cyclic AMP and protein kinase) were 4-6 times more sensitive to inhibition by oleoyl CoA than were nonactivated preparations. An increase in cellular levels of fatty acyl coenzyme A could, therefore, contribute to the feedback inhibition of lipolysis in adipose tissue.

Acyl Coenzyme A↗
PubMed1984

Hormonal regulation of acid cholesterol ester hydrolase activity: effects of triiodothyronine and 17 alpha-ethynylestradiol.

Cholesterol ester hydrolase activity was measured in isolated rat hepatocytes and adipocytes. Administration of triiodothyronine to rats resulted in a specific and selective increase in lysosomal acid (pH 4.5) cholesterol ester hydrolase activity in hepatocytes. Since the majority of lipoprotein degradation occurs in liver parenchymal cells (hepatocytes), the stimulation of liver (hepatocyte) acid cholesterol ester hydrolase activity by triiodothyronine could contribute to the hypocholesterolemic action of thyroid hormones. Treatment of rats with 17 alpha-ethynylestradiol to increase the hepatic degradation of lipoprotein did not change acid cholesterol ester hydrolase activity in liver, indicating that the thyroid hormone induced stimulation of acid cholesterol ester hydrolase activity in hepatocytes is not a secondary effect owing to the increased hepatic catabolism of low density lipoproteins (LDL). In contrast to the results with hepatocytes, hyperthyroidism did not increase acid cholesterol ester hydrolase activity in rat adipocytes.

Acetylglucosaminidase↗
PubMed1983

Correlation of membrane phosphorylation and epidermal growth factor binding to hepatic membranes isolated from triiodothyronine-treated rats.

The in vivo administration of L-triiodothyronine to normal adult rats produced a reduction in the number of binding sites in hepatic membranes for epidermal growth factor; hyperthyroidism had no effect on insulin binding. The decreased receptor number correlated with a decrease in epidermal growth factor-stimulated phosphorylation of isolated hepatic membrane proteins (180 and 165 kDa) with adenosine [gamma-32P]triphosphate.

Animals↗
PubMed1982

Effect of hyperinsulinemia on acid cholesterol ester hydrolase activity in liver, heart and epididymal fat pad preparations from rats and mice.

The effect of insulin on lysosomal acid cholesterol ester hydrolase activity was studied in liver, heart and fat pad preparations from rats and mice. Hyperinsulinemia was induced for a period of 6 days in rats by the subcutaneous administration of exogenous insulin by an osmotic minipump. The effect of more chronic endogenous hyperinsulinemia was studied using genetic strains of diabetic (db/db) mice at 12 weeks of age. Mouse liver and heart preparations were characterized as having an acid pH optimum of 4.5-5 for cholesterol ester hydrolase activity; a smaller but distinct pH optimum could also be observed at pH 7. In contrast, hydrolase activity in mouse fat pad preparations had only one distinct pH optimum of 6.5. Hyperinsulinemia in rats and mice resulted in a significant decrease in acid cholesterol ester hydrolase activity in heart preparations, but had no consistent effect on acid hydrolase activity observed in liver and fat pad preparations. This decrease in lysosomal acid cholesterol ester hydrolase activity in cardiac tissue due to hyperinsulinemia cannot be related to any changes in lipoprotein turnover caused by insulin or diabetes.

Adipose Tissue↗
PubMed1982

Properties of acid and neutral cholesterol ester hydrolases in rat and pigeon aortas.

The activity of cholesterol ester hydrolase was measured in subcellular fractions from rat and pigeon aortas using a glycerol-dispersed cholesterol oleate substrate preparation. The specific activity of acid cholesterol ester hydrolase (assayed at pH 5) in adventitia tissue fractions was 40-50 fold greater than in media-intima fractions from rat aorta. Soluble and particulate subcellular fractions from rat aorta (media-intima) were observed to have cholesterol ester hydrolase activity with both an acid (pH 4.5-5) and a neutral (pH 7.5) pH optimum. A comparison of the subcellular distribution of acid cholesterol ester hydrolase with the lysosomal marker enzyme, N-acetylglucosaminidase, suggests that the acid hydrolase activity originated in aortic lysosomes; the neutral cholesterol ester hydrolase was predominantly soluble. Acid and neutral cholesterol ester hydrolases could also be distinguished on the basic of the effects of Mg Cl2 and NaCl on hydrolase activity and on rates of thermal denaturation. Both acid an neutral hydrolases from rat aorta (media-intima) were inhibited by chloroquine (half-maximal at 2-4 mM), and both hydrolases were characterized as having the same apparent affinity for the glycerol-dispersed cholesterol oleate substrate. Acid and neutral cholesterol ester hydrolases were also observed in preparations from pigeon aortas. The specific activity for both acid and neutral hydrolases was higher in atherosclerosis-susceptible White Carneau pigeon aortas in comparison to Show Racer pigeon aortas.

Animals↗
PubMed1982

Extended chain analogs of [arginine8]vasopressin as model prohormones: investigation of precursor-processing enzymes in extracts of the rat hypothalamus and neural lobe.

Analogs of [arginine8]vasopressin (AVP) in which the peptide chain was elongated from the N-terminus by the addition of Ala-Arg-Arg-, Ala-Ala-Phe-, Pro-Arg-Val-, Pro-Ala-Arg-Arg, and Pro-Ala-Ala-Phe-, and from the C-terminus by the addition of -Ala-Met-Ala-NH2 and -Gly-Arg-Arg-Ala-NH2 were synthesized by the solid phase method and purified by Sephadex G-15 chromatography. At the final step of the synthesis, the extent of formation of the intramolecular disulfide bond was found to be sequence dependent. These peptides were incubated with extracts of the rat hypothalamus (supraoptic region) and neural lobe and with isolated neurosecretory granules from the neural lobe, and the release of vasopressin was measured by the rat pressor assay. All peptides resisted conversion to the hormone in the presence of tissue extracts, except (Ala-Ala-Phe)-AVP which was converted to AVP in the presence of all three tissue extracts at pH 4.7 but not at pH 8.0. When these peptides were treated with trypsin, chymotrypsin, or leucine aminopeptidase at pH 8.0, only the action of chymotrypsin on [Ala-Ala-Phe]AVP resulted in AVP formation. Evidence obtained using lysosomal enzyme markers suggested that the converting enzyme activity in neurosecretory granule preparations was not of lysosomal origin.

Amino Acid Sequence↗
PubMed1981

Studies on the activity of acyl-CoA:cholesterol O-acyltransferase and acid cholesterol ester synthetase in rat aortas.

Acyl-CoA: cholesterol O-acyltransferase (ACAT) activity was measured in microsomal preparations from rat aorta (intima-media) with [14C]oleoyl CoA and endogenous cholesterol as substrates. The specific activity of ACAT in liver and adrenal microsomal preparations was 10--20-times greater than ACAT activity in aortic microsomes; no ACAT activity could be detected in fat pad microsomes. ACAT activity in liver and adrenal microsomes was enhanced by the addition of exogenous cholesterol. In contrast, exogenous cholesterol did not increase ACAT activity in rat aortic microsomes. Levels of endogenous cholesterol and ACAT activity in microsomal preparations from rat aorta were not reduced when circulating plasma cholesterol levels were decreased by the administration of 4-aminopyrazolopyrimidine to rats. Acid cholesterol ester synthetase activity was not detectable in high-speed supernatant fractions from rat aorta; low levels of activity could be measured in rat aorta microsomal preparations but this was less than 10% of ACAT activity. Thus, ACAT would seem to be the principal enzymatic route for the synthesis of cholesterol esters in aorta.

Acyltransferases↗
PubMed1981

Effect of thyroid hormones on acid cholesterol ester hydrolase activity in rat liver, heart and epididymal fat pads.

The regulation of acid cholesterol ester hydrolase activity by thyroid hormones was studied in subcellular fractions from rat liver, heart, and epididymal fat pads; hydrolase activity was determined at pH 5 with a glycerol-dispersed cholesterol oleate substrate preparation. Acid cholesterol ester hydrolase activity was decreased in liver preparations from thyroidectomized rats relative to activity in livers from euthyroid control rats. Administration of triiodothyronine to either euthyroid or hypothyroid (thyroidectomized) rats resulted in an increase in acid cholesterol ester hydrolase activity in liver preparations. Similar effects of thyroidectomy and the administration of triiodothyronine on acid cholesterol ester hydrolase activity were observed with fat pad preparations. In contrast, no effect of thyroid hormones was observed on acid cholesterol ester hydrolase activity in heart. These results suggest that thyroid hormones may regulate the catabolism of serum lipoproteins, in part, by alterations in lysosomal acid cholesterol ester hydrolase activity in liver and epididymal fat pads.

Acetylglucosaminidase↗
PubMed1980

Properties of a phosphoprotein phosphatase from rat epididymal fat pads: deactivation of hormone-sensitive triglyceride lipase and activation of glycogen synthase in adipose tissue.

A phosphoprotein phosphatase has been partially purified from rat epididymal fat pads by a procedure utilizing ammonium sulfate and ethanol precipitations and chromatography on DEAE-Sephadex A-50. The phosphatase was eluted from Sephadex G-75 columns with an apparent molecular weight of 28 000. The phosphoprotein phosphatase catalyzed the reversible deactivation of protein kinase activated chicken adipose tissue hormone-sensitive triglyceride lipase. Phosphatase activity measured with activated triglyceride lipase as substrate was completely dependent upon the presence of metal ions (Mg2+, Ca2+, or Mn2+) and was inhibited by inorganic phosphate and adenine nucleotides. The fat pad phosphatase increased the rate of activation of glycogen synthase in rat adipose tissue infranatant fractions from fed and 24-h fasted rats but had little or no effect on synthase activity in infranatant fractions from rats fasted for 48 h. Fasting had no effect on rat fat pad phosphatase activity measured with triglyceride lipase as substrate, but phosphatase activity was decreased in preparations from diabetic rats.

Animals↗
PubMed1978

Characterization of cholesterol ester hydrolase activities in rabbit and guinea pig aortas.

Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit).

Animals↗