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Biomedical subjects

R J Morin

Publications and source records attributed to R J Morin.

At least 37 records · Page 2Linked to original sources
PubMed1985

Influence of cholesterol oxidation derivatives on membrane bound enzymes in cultured aortic smooth muscle cells.

Cholestane-3 beta, 5 alpha, 6 beta-triol and 25-hydroxycholesterol are two of the most cytotoxic and also relatively abundant of the autoxidation derivatives of cholesterol. Cultured aortic smooth muscle cells which were incubated with 10 micrograms/ml of either sterol for 24 to 48 hr showed a marked decrease of 5'-nucleotidase activity in isolated crude membranes. It was further demonstrated that 5'-nucleotidase activity was also markedly decreased in plasma membrane-enriched fractions when cells were incubated with cholestane-3 beta,5 alpha,6 beta-triol. Na+,K+-ATPase activity in crude membranes showed a significant decrease (32%) only in cells incubated with cholestane-3 beta,5 alpha,6 beta-triol for 48 hr. There was no effect on Na+,K+-ATPase activity in cells incubated for 24 hr with either sterol.

5'-Nucleotidase↗
PubMed1985

Effects of oxygenated derivatives of cholesterol on cholesterol uptake by cultured aortic smooth muscle cells.

The cytotoxicity of oxygenated derivatives of cholesterol on the cultured cells may not only be due to their potent inhibition of cholesterol biosynthesis, but also could be related to their capability for inhibiting cholesterol uptake from exogenous sources, particularly in arterial cells, which synthesize cholesterol at a very slow rate. In cultured aortic smooth muscle cells, the most potent inhibitor of cholesterol uptake was cholestane-3 beta,5 alpha,6 beta triol, which at 100 micrograms/ml medium reduced uptake of cholesterol to 10% of the control. The next most potent inhibitors were 5 alpha,6 alpha- epoxycholesterol and 25-hydroxycholesterol, which reduced uptake of cholesterol to 60%. 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol inhibited cholesterol uptake to 30-50%. A consequence of their inhibitory effects on cholesterol uptake could be a depletion of cell membrane cholesterol, resulting in alterations in membrane structure and function and eventually in cell death.

Animals↗
PubMed1984

Modulation of 3-hydroxy-3-methyl glutaryl CoA reductase by 2,3-diphosphoglyceric acid.

Rat liver microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was activated by 50% at a concentration of 0.4 mM 2,3-diphosphoglyceric acid (DPG) and by 11-fold at 10 mM DPG. DPG also prevented the inactivation of HMG-CoA reductase by ATP and Mg++. Rat liver microsomal HMG-CoA reductase prepared in the presence of 1 mM DPG was significantly more active than when prepared in the absence of DPG. Activation of the enzyme by DPG and protection of the enzyme against inhibition by ATP and Mg++ by DPG were also observed with solubilized HMG-CoA reductase.

2,3-Diphosphoglycerate↗
PubMed1984

Inhibition of human lecithin cholesterol acyltransferase by monoterpenes.

The lecithin-cholesterol acyltransferase activity of human plasma was found to be inhibited by Rowachol, a proprietary mixture of pure monoterpenes. Menthol, the major ingredient in Rowachol (32%), and a number of other monoterpenes were found to inhibit the enzyme independently. Concentrations of monoterpenes required to achieve 50% inhibition were of the same order of magnitude as the cholesterol concentration present in the reaction mixture.

Camphor↗
PubMed1984

Effects of cholesterol autoxidation derivatives on hexose transport in cultured aortic smooth muscle cells.

Several cholesterol autoxidation derivatives known to be cytotoxic to arterial smooth muscle cells both in vivo and in vitro were shown to inhibit hexose transport in these cells in culture. Cholestane-3 beta, 5 alpha, 6 beta-triol was the most potent inhibitory sterol. The rapid onset of inhibition (15 min) and the reversibility of the effect upon removal of the sterol from the tissue culture medium suggests that the effect may be due to incorporation of the sterol into the plasma membrane. 25-Hydroxycholesterol, a potent inhibitor of sterol biosynthesis in cultured arterial smooth muscle cells, did not affect hexose transport up to 8 hr of incubation. The cytotoxic effect of 25-hydroxycholesterol, therefore, may be a consequence of the reduced sterol biosynthesis caused by this sterol.

Animals↗
PubMed1982

Effect of age and cholestyramine feeding on rat liver 3-hydroxy-3-methyl glutaryl CoA reductase, sterol carrier protein 1 and sterol carrier protein 2 activities.

The rate of formation of sterol from squalene in livers from suckling rats was less than one-third that of adults. This difference was due to a lesser activity of microsomal enzymes in the suckling rat livers, and not to any difference in cytosolic sterol carrier protein 1. The microsomal enzymes and sterol carrier protein 2 of the cytosol required for the conversion 7-dehydrocholesterol to cholesterol were both lower in suckling rats compared to adults. Both those activities paralleled the differences in HMG-CoA reductase activities between suckling and adult rats. Feeding of cholestryamine to adult rats increased the activities of the microsomal enzymes, sterol carrier protein 1 and sterol carrier protein 2 involved in the conversion of squalene to cholesterol.

Administration, Oral↗
PubMed1982

Relationships between circadian cycles of rat adrenal cholesterol ester metabolizing enzymes, cholesterol, ascorbic acid, and corticosteroid secretion.

The circadian changes in rat adrenal cholesterol ester (CE) metabolism have been studied and related to the circadian changes in adrenal ascorbic acid and corticosterone levels and plasma corticosterone levels. Significant declines in the ratio of CE/C, cholesterol esterase (CEase) and acyl CoA:cholesterol acyl transferase (ACAT) activities occur during the peak and declining phases of adrenal and plasma corticosteroids, suggesting that when there is a decreased need for steroid precursors the amount of stored CE is decreased, and that the enzymes involved in CE metabolism decline in activity. Adrenal ascorbic acid has a biphasic rhythm with peaks at 0900 and 2200 h. The rhythm of ascorbic acid appears to be inverse to that of ACAT activity, suggesting possible relationships between the two parameters.

Acyltransferases↗
PubMed1981

A lipoprotein independent assay for human serum lecithin-cholesterol acyltransferase.

A method has been developed for estimation of human serum lecithin-cholesterol acyltransferase free of interference by endogenous lipoproteins. Precipitation of serum low and very low density lipoproteins by sodium phosphotungstate and magnesium chloride results in complete recovery of lecithin-cholesterol acyltransferase activity in the supernatant. One microliter of the supernatant can be accurately assayed with a highly efficient substrate containing phosphatidylcholine-cholesterol vesicles and apo-high density lipoproteins (HDL), with no interference from endogenous HDL or residual precipitation reagents. Serum levels of the enzyme were found to be reduced in patients with parenchymal liver disease, renal disease, gastrointestinal tumors and anemias.

Disease↗
PubMed1981

Effect of buffer constituents on rat liver 3-hydroxy-3-methyl glutaryl coenzyme A reductase.

Rat liver microsomes prepared in Tris buffer exhibited 3 to 10 times higher 3-hydroxy-3-methyl glutaryl CoA reductase specific activity than microsomes prepared with potassium phosphate buffer. This higher activity was observed in rats killed during mid-light cycle, but microsomes from rats killed during mid-dark cycle showed no significant difference in enzyme activity between buffers. When microsomes prepared in the 2 different buffers were preincubated with ATP and MG++, enzyme activity was inhibited to the same extent. The cytosol fraction in each of the 2 different buffer preparations possessed similar phosphatase activity. The higher 3-hydroxy-3-methyl reductase activity in Tris buffer, therefore, does not appear to be due to differences in phosphorylation or dephosphorylation activity.

Adenosine Triphosphate↗
PubMed1980

Inhibition of rat hepatic sterol formation from squalene by plasma lipoproteins.

The conversion of 3H-squalene to sterols by rat liver microsomes and cytosol was inhibited by individual rat and human plasma lipoproteins at various concentrations. This inhibition was also observed with added human high density apolipoprotein, but triglycerides, cholesterol, or cholesteryl esters had no inhibitory effects. Lipoproteins and apo high density lipoprotein (HDL) were demonstrated to bind 3H-squalene in vitro. The binding of 3H-squalene by apo HDL could be reversed by increasing concentration of liver cytosol containing sterol carrier protein.

Animals↗
PubMed1980

Effect of uremia on incorporation of acetate into rat plasma and tissue lipids.

Experimental uremia was induced in rats by means of bilateral nephrectomy or bilateral ureteral ligation. Incorporation of acetate-1-14C into expired 14CO2 and into plasma and tissue lipids was studied immediately after surgery and at 48 hr, when the rats were uremic. In rats studied immediately after surgery, bilateral nephrectomy, but not bilateral ureteral ligation, significantly decreased the conversion of acetate-1-14C into expired 14CO2. In uremic rats at 48 hr, acetate-1-14C metabolism to 14CO2 was not significantly altered in either group. Plasma triglyceride concentrations and 14C-acetate incorporation into triglycerides were increased in the 48-hr uremic groups, but plasma and liver triglyceride specific radioactivities were not significantly altered. Plasma free fatty acid concentrations and incorporation of acetate into free fatty acids were lower in the 48-hr uremic groups than in controls. Plasma cholesterol concentrations and specific radioactivities were increased in these uremic groups, as were liver free cholesterol specific activities. These results suggest that increased triglyceride and cholesterol synthesis from acetate may contribute to the hypertriglyceridemia and hypercholesterolemia observed in uremic rats.

Acetates↗
PubMed1980

Effect of hemodialysis with acetate vs bicarbonate on plasma lipid and lipoprotein levels in uremic patients.

A group of 18 stable hemodialysis patients were dialyzed alternately for 4 week periods against acetate or bicarbonate solutions. Total plasma cholesterol and triglyceride concentrations and the content of these lipids in the VLDL, LDL, and HDL lipoprotein fractions were not significantly different when these dialysis periods were compared. When patients were subgrouped according to whether they were normo or hypertriglyceridemic or whether they had an adequate or deficient lipolytic response to heparin infusion, there were also no differences apparent between the acetate vs. bicarbonate dialysis periods. The data indicates, therefore, that acetate is probably not a contributory factor to the hypertriglyceridemias observed in some chronic hemodialysis patients.

Acetates↗
PubMed1980

Effects of dietary ascorbic acid and vitamin E deficiency on rat adrenal cholesterol ester metabolism and corticosteroidgoenesis.

The effect of dietary ascorbic acid (AA) and deficiency of vitamin E, alone and in combination, upon adrenal steroidogenesis in rats have been tested in vivo. High concentrations of AA blocked the normal stress-induced increase in plasma and adrenal corticosteroid concentration. Adrenal cholesterol ester hydrolase activity was also markedly inhibited by the high AA diet, while acylcoenzyme A:cholesterol acyltransferase was significantly increased. Vitamin E deficiency caused generally opposite effect, while simultaneous excess AA and vitamin E deficiency caused these parameters to return toward control values. Thus the role of AA in blocking adrenal steroidogenic response to stress is confirmed. It's mode of action may be at least partly through control of cholesterol availability for steroidogenesis.

Adrenal Glands↗
PubMed1980

In vitro conversion of squalene from squalene-phospholipid liposomes into sterols by rat liver microsomes and cytosol.

When rat liver cytosol, possessing sterol carrier protein (SCP) activity was incubated with [3H]-squalene-phospholipid liposomes, cofactors, and rat liver microsomes, squalene from the liposomes was converted into sterols. When cytosol was omitted from the incubation mixture, only insignificant amounts of sterols were produced. Liposomes of squalene with either phosphatidylserine or phosphatidylcholine were equally effective as substrates. The liposomes were stable at 4 degrees C for 3 weeks. The ratio of squalene to phospholipid in the liposomes could be varied over a range of 0.004 to 0.23. Multilamellar liposomes with squalene were not effective as a substrate for the conversion of squalene to sterols. The mechanism for transfer of squalene from the liposomes to the enzymes appears to be initial binding of liposomes to microsomes, with subsequent transfer of the substrate to the enzyme site by the SCP in the cytosol. Microsome-liposome complexes prepared in the absence or presence of cytosol are effective in converting squalene to sterols only if cytosol is added again, indicating that cytosol is not required for the binding of liposomes to microsomes.

Animals↗