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Biomedical subjects

K R Norum

Publications and source records attributed to K R Norum.

At least 127 records · Page 7Linked to original sources
PubMed1979

Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro.

1. The uptake of 125I-labelled high density lipoproteins (HDL) in various organs of the rat was determined after an intravenous injection. The uptake of 125I-labelled polyvinylpyrrolidone in the same organs was determined in order to assess uptake by fluid endocytosis. The uptake/organ was highest for the liver. The adrenals showed the highest uptake/unit weight of the organs studied. The liver, the kidneys and the spleen showed comparable values for uptake/g of tissue. The uptake of 125I-labelled HDL exceeded by far that of 125I-labelled polyvinylpyrrolidone in the liver, the kidneys, the spleen and the adrenals, indicating that the uptake of 125I-labelled HDL was mediated by adsorptive endocytosis. 2. The in vivo uptake of 125I-labelled HDL was determined in purified hepatocytes and non-parenchymal cells prepared by collagenase perfusion of livers from animals after intravenous injections of 125I-labelled HDL. When expressed per cell, the hepatocytes and the non-parenchymal liver cells took up about the same amount of 125I-labelled HDL. 3. The in vitro uptake and degradation of 125I-labelled HDL in isolated rat hepatocytes was studied. The uptake at increasing concentrations of 125I-labelled HDL was saturable indicating uptake mediated through binding sites. 125I-labelled HDL were easily degraded by contaminating proteases from the perfusate. 4. Subcellular fractionation by isopycnic centrifugation indicated that the accumulation of 125I-labelled HDL did not take place in the lysosomes, but rather on the plasma membrane and possibly in the endosomes (phagosomes). 5. 125I-labelled HDL were internalized into the cells and degraded in the lysosomes. Leupetin and chloroquine, inhibitors of the lysosomal function effectively inhibited the formation of 125I-labelled acid-soluble radioactivity by the cells. Chloroquine, but not the protease inhibitor leupeptin, reduced the hydrolysis of the cholesteryl ester moiety of HDL.

Animals↗
PubMed1979

Intracellular localization and degradation of asialofetuin in isolated rat hepatocytes.

Analysis by isopycnic and differential centrifuging of the intracellular distribution of radioactivity following uptake of 125I-labelled asialofetuin by isolated rat hepatocytes showed that during incubations up to 1 h, most of the radioactivity was associated with structures which had a subcellular distribution pattern different from both the lysosomes and the plasma membrane. The latter two organelles were followed by means of enzyme markers. Ca2+ is necessary for the binding of asialofetuin to the plasma membrane, and it was also possible to differentiate between asialofetuin bound to the plasma membrane and that contained in intracellular structures by removing Ca2+ from the medium (by EGTA). Such experiments showed that asialofetuin became rapidly internalized. Practically all the labelled protein was located intracellularly in cells that had been incubated with asialofetuin for more than 30 min. When incubations were carried out for more than 1 h a peak appeared in the radioactivity distribution in the same place as the peak of activity of lysosomal marker enzymes. However, degradation of asialofetuin takes place in the lysosomes and this starts before the labelled protein can be found in the lysosomal fractions. Our data suggest that the rate-determining step in the cellular handling of asialofetuin is the transport of endocytized protein from the endocytic vesicles to the lysosomes.

Animals↗
PubMed1979

Effect of marine oil and rapeseed oil on composition of fatty acids in lipoprotein triacylglycerols from rat blood plasma and liver perfusate.

The fatty acid patterns of triacylglycerols (TG) from very low density lipoprotein (VLDL) in blood plasma and liver-perfusate from rats fed partially hydrogenated marine oil or rapeseed oil were determined. In the plasma from rats fed rapeseed oil for three days and three weeks, there was a small but significant decrease in the percentage of 22:1 fatty acid from 17.2 to 11.2% with length of feeding. In liver-perfusate, the comparable decrease with dietary rapeseed oil was from 18.5 to 5.2%, and with dietary marine oil from 13.4 to 8.0%. In contrast to the liver-perfusate, the remaining liver had only a very low 22:1 composition (ca 2%) independent of feeding period or diet. The results indicated that the liver exported the very long chain fatty acids and that an adaptation took place after three days feeding with rapeseed oil or marine oil. This adaptation in the liver could possibly explain why TG accumulation in hearts, which appears after three days' feeding with rapeseed oil or marine oil, disappears after an extended feeding period.

Animals↗
PubMed1979

Esterification of cholesterol in fish plasma: studies on the cholesterol esterifying enzyme in plasma of char (Salmo alpinus L.).

1. Plasma of sea char (Salmo alpinus L.) has the ability to esterify cholesterol in vitro. Heat inactivation of the plasma totally inhibited the esterification. 2. Arrhenius plot of the esterification of [3H]cholesterol was linear in the temperature range 5-35 degrees C. 3. Cholesterol esterification in sea char plasma could not be reversibly inhibited by sulphydryl-blocking agents. Total equilibration of the added [3H]cholesterol and the endogenous cholesterol could therefore not be obtained. 4. Comparison of esterification of endogenous and labelled cholesterol revealed that the isotopic method was valid only in qualitative measurements.

Animals↗
PubMed1979

Influence of cholesterol/fat feeding on cholesterol esterification and morphological structures in intestinal mucosa from guinea pigs.

Guinea pigs were fed a semisynthetic diet containing 10% (by weight) cottonseed oil and 1% cholesterol. In response to cholesterol/fat feeding there was an increase in both the unesterified cholesterol (UC) and cholesteryl ester (CE) of the intestinal mucosal cell. Along with the increased cholesterol levels there was a 4-fold increase in the microsomal acylCoA:cholesterol acyltransferase (ACAT) activity after only two days of cholesterol/fat feeding. After 6 days on the experimental diet the ACAT activity was up to 8-fold the activity of the control, and then remained at this level for up to 20 days. The increased ACAT activity was probably not due to increased substrate concentration alone, since the fractional esterification of cholesterol also increased when the cholesterol/fat containing diet was given. There was also an increase in the triglyceride content of the intestinal mucosal cells from guinea pigs on the experimental diet. The mucosal cells of the cholesterol/fat fed animals accumulated varying amounts of lipid droplets, which were without an enveloping membrane, suggesting that the uptake of lipids from the intestinal lumen was higher than the capacity to synthesize and/or secrete lipoproteins. Simultaneously the size and amount of secondary lysosomes increased. A considerable increase in lipid droplets, lipolysosomes, and residual bodies was observed in the lamina propria macrophages while no crystalline clefts were seen.

Animals↗
PubMed1979

Esterification of cholesterol in human small intestine: the importance of acyl-CoA:cholesterol acyltransferase.

Human intestinal mucosa contains acyl-CoA:cholesterol acyltransferase activity. The enzyme has been studied by using oleylcarnitine, CoA and carnitine palmitoyltransferase as an oleyl-CoA regenerating system. The enzyme was found in the particulate fraction of the cells, it had a pH optimum between 7.2 and 8.2, and was inhibited by taurocholate. The specific enzymic activity in biopsies from intestinal mucosa of normal men was found to be 3.6 +/- 1.37 nmol cholesteryl ester formed mg protein-1 h-1, an activity which can account for all cholesteryl esters in intestinal lymph. Low enzymic activity was found in biopsies from patients with small intestinal disorders. Two pancreatectomized patients had values within the normal range.

Acyltransferases↗
PubMed1979

The hepatic secretion of lecithin: cholesterol acyltransferase in rats with increased secretion of triglycerides due to ventromedial hypothalamic lesions.

Lecithin:cholesterol acyltransferase (LCAT) is postulated to take care of excess cholesterol formed during metabolism of triglyceride (TG)-rich lipoproteins. To test this hypothesis the relationship between secretion of LCAT and TG have been investigated in rats with ventromedial hypothalamic lesions which lead to increased hepatic secretion of TG. 1. The increased plasma concentration of TG in rats with ventromedial hypothalamic lesions was positively correlated to the activity of LCAT in plasma. 2. Incubation of hepatocytes isolated from such rats revealed a positive linear correlation between secretion of TG and of LCAT. 3. The secretion of unesterified cholesterol was neither correlated to the secretion of the acyltransferase nor to the TG.

Animals↗
PubMed1979

High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study.

The high density lipoprotein (HDL) cholesterol concentrations of frozen specimen obtained in 1972-73 are reported from 93 men aged 40-49 years who later developed coronary heart disease (CHD), and for 186 controls. Mean HDL cholesterol of CHD-patients was 7.9% lower than that of controls matched for smoking habits and serum concentrations of triglycerides and total cholesterol (p 0.05 for 82 men who had myocardial infarction, n.s. difference for 11 with sudden coronary death), and 10.2% lower (p 0.05) than that of controls who were not matched for the parameters mentioned. The present prospective study confirms that HDL cholesterol is inversely associated with the risk of developing CHD in middle-aged men.

Adult↗
PubMed1978

Lecithin:cholesterol acyltransferase activity in rats treated with 4-amino-pyrazolo-pyrimidine.

Lecithin:cholesterol acyltransferase(LCAT) in rats treated with 4-amino-pyrazolo-pyrimidine (4-APP) has been studied. Treatment with 4-APP decreased the plasma concentration of triglycerides, cholesterol and cholesteryl ester concomitantly with a decreased rate of cholesterol esterification in plasma. The reduced cholesterol esterification was due both to an effect on the enzyme and on the lipoprotein substrate. Plasma prothrombin decreased to the same extent as that of LCAT, indicating that the primary effect of 4-APP is upon protein synthesis and secretion from the liver.

Adenine↗
PubMed1978

Intestinal lymph chylomicron cholesteryl ester during duodenal triolein infusion at increasing rate.

Chylomicron lipid composition in mesenteric lymph fistula rats was followed during duodenal triolein infusion at three rates. Esterified cholesterol decreased progressively in all groups as triglyceride transport continued, and the rate of decrease was reciprocally related to the triolein infusion rate. Suppression of cholesterol ester synthesis may spare unesterified cholesterol for chylomicron membrane formation. Ratios of triglyceride to phospholipid and to unesterified cholesterol increased with the duration of triglyceride secretion, while the chylomicron surface lipid composition remained constant over time. The rate of increase in the core:surface lipid ratios was the same irrespective of the triolein transport rate.

Animals↗
PubMed1978

Aspects of the role of lecithin:cholesterol acyltransferase in metabolism of triglycerides.

An increased TG secretion from the liver may lead to an increased secretion of LCAT. Studies on isolated rat hepatocytes have shown: 1. Oleic acid added to the medium stimulates TG and LCAT secretion in a similar way. 2. Cycloheximide, colchicine, 4-amino-pyrazolopyrimidine, and D-galactosamine depress the secretion of both TG and LCAT. 3. There is a positive linear correlation between TG and LCAT secretion in cell preparations from rats operated on with ventromedial hypothalamic lesions. Treatment of rats with orotic acid resulted in maintained plasma LCAT activity despite very low TG concentration. This indicates that LCAT secretion is not dependent upon an intact TG secretion.

Animals↗
PubMed1977

Uptake and degradation of 125I-labelled asialo-fetuin by isolated rat hepatocytes.

125I-Labelled asialo-fetuin was taken up by isolated rat hepatocytes by a saturable process. Half maximum uptake was seen at about 3 - 10(-8) M asialo-fetuin. Non-parenchymal liver cells did not take up asialo-fetuin in vitro. Rate of uptake of asialo-fetuin exceeded rate of degradation at all concentrations of asialo-fetuin tested. Asialo-fetuin consequently accumulated in the cells until the extracellular supply was exhausted. Asialo-fetuin degradation could be studied without concurrent uptake by incubating cells, previously exposed to asialo-fetuin, in asialo-fetuin-free medium. Degradation, as evidenced by increase in acid-soluble radioactivity, was inhibited by NH4Cl and chloroquine. The change with time in the intracellular distribution pattern of radioactivity in cells that had been exposed to 125I-labelled asialo-fetuin for 10 min was examined by means of differential centrifugation. Initially, the radioactivity was found mostly in the microsomal fraction. 60 min after the exposure to labelled protein, the distribution pattern of radioactivity resembled that of the lysosomal enzyme beta-acetylglucosaminidase. The possibility that asialo-fetuin digestion takes place in lysosomes is discussed.

Ammonium Chloride↗