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J J Volpe

Publications and source records attributed to J J Volpe.

At least 181 records · Page 10Linked to original sources
PubMed1978

Regulation of cholesterol ester synthesis in cultured glial and neuronal cells. Relation to control of cholesterol synthesis.

Regulation of cholesterol ester synthesis was studied in cultured C-6 glial and neuroblastoma cells. Particular emphasis was placed on the relation of this regulation to control of cholesterol synthesis. The effectors studied were low density lipoprotein (LDL) and desmosterol. Distinct differences in regulation were observed between the glial and neuronal cells. In the neuronal cells cholesterol ester synthesis (from [14C]oleate) was not affected by even high concentrations of LDL or desmosterol. In contrast, cholesterol ester synthesis was stimulated as much as 12-fold in the glial cells after just 5 h exposure to LDL or desmosterol. Cholesterol synthesis (from [14C]acetate) was inhibited in a simultaneous and quantitatively similar manner. Suitable experiments indicated that alterations in pool sizes of intermediates did not contribute to the genesis of the observed responses and suggested that LDL and desmosterol produced their effects by stimulating esterification of primarily endogenous cholesterol. The data may have major implications concerning the controlling metabolic events prior to and at the onset of myelination.

Acetates↗
PubMed1977

Cholesterol biosynthesis and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase in cultured glial and neuronal cells. Regulation by lipoprotein and by certain free sterols.

Regulation of cholesterol synthesis and, particularly, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was studied in C-6 glial and neuroblastoma cells. Comparison of rates of incorporation of radioactivity from [14C]-acetate or [3H]mevalonate into digitonin-precipitable sterols indicated that HMG-CoA reductase is the major rate-limiting enzyme in cholesterol biosynthesis in both cell types. HMG-CoA reductase exhibited marked changes in enzymatic activity according to the lipoprotein content of the medium. However, significant differences were observed between the two cell types in the quantitative and temporal aspects of this regulation. Thus, in C-6 glial cells, when total serum lipoprotein was removed from the medium, reductase activity increased by 7-8-fold between 2 and 6 h later. After 24 h reductase activity in cells grown in lipoprotein-poor serum was 20-fold higher than in cells grown in regular serum. In neuroblastoma cells, under similar conditions, reductase activity did not increase at all until cells were in lipoprotein-poor serum for more then 6 h, and after 24 h, enzyme activity in cells grown in lipoprotein-poor serum was only approx. 3-fold higher than that in cells grown in regular serum. Addition of total serum lipoprotein caused a rapid decline in enzymatic activity in both cell types, with a t1/2 of 2-2.5 h; however, the onset of the decline was immediate in the glial cells but delayed 1-1.5 h in the neuronal cells. The critical regulatory component in the total lipoprotein fraction was shown to be contained in the low density lipoproteins for the reductase of both cell types. Regulation of reductase by free sterols was shown in both the glial and neuronal cells. However, effects were more marked and evolved more rapidly in the glial cells. The data thus provide important insight into the regulation of cholesterol synthesis in two cell types which are considered to be good models of neurons and glia of developing brain. The occurrence of more marked and more rapid regulation in the glial than in the neuronal cells is compatible with the important role glia play in brain lipid synthesis. The demonstration of dramatic regulation of HMG-CoA reductase by desmosterol, a sterol found in high concentration in brain early in development, may indicate a heretofore unrecognized role for this sterol in the regulation of cholesterol biosynthesis during maturation. 7-Ketocholesterol was shown to induce in C-6 glial cells a rate of decline of HMG-CoA reductase activity compatible with a t 1/2 of just 20 min. This extremely rapid rate of decline suggests that the effect involves an alteration in catalytic efficiency of the enzyme. The mechanism of this effect remains to be determined.

Alcohol Oxidoreductases↗
PubMed1977

Ventricular dilation preceding rapid head growth following neonatal intracranial hemorrhage.

We describe two patients in whom ventricular dilation began within a week of neonatal intraventricular hemorrhage and preceded rapid head growth and clinical signs of increased intracranial pressure by days to weeks. The posthemorrhagic ventricular dilation is readily demonstrated in the neonatal period by computerized tomography of the cranium. These data indicate the importance of careful follow-up of survivors of intraventricular hemorrhage, early demonstration of ventricular dilation and prompt therapeutic intervention to prevent brain injury.

Cephalometry↗
PubMed1977

Neonatal seizures.

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Action Potentials↗
PubMed1976

Long-term regulation by theophylline of fatty acid synthetase, acetyl-CoA carboxylase and lipid synthesis in cultured glial cells.

The long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase and of fatty acid and sterol synthesis was studied in C-6 glial cells in culture. When theophylline (10(-3) M) was added to the culture medium of these cells, rates of lipid synthesis from acetate and activities of synthetase and carboxylase became distinctly lower than in cells that were untreated. This effect appeared after approximately 12 h, and after 48 h enzymatic activities were reduced approx. 2-fold and rates of lipid synthesis from acetate 3- to 4-fold. The likelihood that the decrease in fatty acid synthesis from acetate was caused by the decrease in activities of fatty acid synthetase and acetyl-CoA carboxylase was established by several observations. These indicated that the locus of the effect probably did not reside at the level of acetate uptake into the cell, alterations in acetate pool sizes or conversion of acetate to acetyl-CoA. Moreover, de novo fatty acid synthesis was found to be the predominant pathway in these glial cells, whether treated with theophylline or not. The mechanism of the effect of theophylline on fatty acid synthetase was shown by immunochemical techniques to involve an alteration in content of enzyme rather than in catalytic efficiency. The change in content of fatty acid synthetase was shown by isotopic-immunochemical experiments to involve a decrease in synthesis of the enzyme. The mechanism whereby theophylline leads to a decrease in lipogenesis and in the synthesis of fatty acid synthetase may not be mediated entirely by inhibition of phosphodiesterase and an increase in cyclic AMP levels, because dibutyryl cyclic AMP (10(-3) M) only partially reproduced the effect.

Acetyl-CoA Carboxylase↗