Search PubMed⌕ Search

Biomedical subjects

A A Spector

Publications and source records attributed to A A Spector.

At least 253 records · Page 14Linked to original sources
PubMed1966

Relationship between fatty acid and glucose utilization in Ehrlich ascites tumor cells.

Glucose greatly increased total free fatty acid (FFA) esterification by Ehrlich ascites tumor cells. However, the FFA concentration of the cells was not altered. Less exogenous FFA was oxidized to CO(2) at any given extracellular FFA:albumin molar ratio when glucose was available, but increasing amounts of radioactive CO(2) were produced as the FFA:albumin molar ratio was raised, even in the presence of glucose. It is suggested that glucose, by providing either energy or an excess of triose acceptor for fatty acid esterification, stimulated FFA uptake only indirectly, by increasing the utilization of FFA subsequent to initial uptake from the medium, i.e., by increasing the turnover rate of the cellular FFA pool. Availability of glucose decreased the oxidation of endogenous lipid radioactivity and the depletion of endogenous lipid ester radioactivity. Most of the radioactivity utilized was derived from phospholipids, and depletion of phospholipid radio-activity was spared when glucose was available. Depletion of cellular total lipid ester also was spared in the presence of glucose. Availability of FFA did not decrease total glucose uptake or its oxidation to CO(2). Glucose utilization by these cells appears not to be regulated by FFA availability in the manner that Randle and coworkers described for muscle.

Animals↗
PubMedDate not supplied

A model for cochlear outer hair cell deformations in micropipette aspiration experiments: an analytical solution.

We propose a mathematical model to describe the deformations of the cochlear outer hair cell (OHC) in the micropipette aspiration experiments. The bending effect is considered, and the OHC is treated as a cylindrical shell. The pipette effect is modeled by two-dimensional normal loading. Considering the OHC wall as an infinitely long cylinder, we obtain solution in terms of Fourier series with respect to the circumferential coordinate where coefficients are expressed by closed formulae. We keep leading terms in Fourier series and derive a closed formula for the length of tongue of the aspirated cell surface in terms of pipette pressure, cell geometry, and elastic moduli. To demonstrate application of the theory, we use data recently reported from the micropipette aspiration experiments and obtain an estimate of the elastic shear modulus for the OHC lateral wall.

Animals↗
PubMedDate not supplied

A model for cochlear outer hair cell deformations in micropipette aspiration experiments: an analytical solution.

We propose a mathematical model to describe the deformations of the cochlear outer hair cell (OHC) in the micropipette aspiration experiments. The bending effect is considered, and the OHC is treated as a cylindrical shell. The pipette effect is modeled by two-dimensional normal loading. Considering the OHC wall as an infinitely long cylinder, we obtain solution in terms of Fourier series with respect to the circumferential coordinate, where coefficients are expressed by closed formulae. We keep leading terms in fourier series and derive a closed formula for the length of tongue of the aspirated cell surface in terms of pipette pressure, cell geometry, and elastic moduli. To demonstrate application of the theory, we use data recently reported from the micropipette aspiration experiments and obtain an estimate of the elastic shear modulus for the OHC lateral wall.

Biomechanical Phenomena↗
PubMedDate not supplied

Fatty acid and lipid composition of the monkey retina in diet-induced hypercholesterolemia.

We determined the fatty acid composition of the lipids of cynomolgus monkey retina in animals fed commercial chow or a saturated fat, cholesterol-enriched atherogenic diet for 100 days. Doxosahexaenoic acid (22 : 6) accounted for 25.8% of the ethanolamine phosphoglyceride fatty acids, 17.6% of the serine plus inositol phosphoglyceride fatty acids, 8.4% of the choline phosphoglyceride fatty acids and 5.8% of the neutral lipid fatty acids in the retinas of the chow-fed animals. Therefore, monkey retinas, like those of other mammalian species, ordinarily contain large amounts of 22 : 6. Retinas from the monkeys fed the atherogenic diet contained less 22 : 6 as well as other polyunsaturates in each of the phospholipid classes. The decrease in polyunsaturates was compensated for by increases in palmitic, stearic, and oleic acids. There was no difference in the amount of phospholipid, the distribution of phospholipid classes, or the amount of cholesterol in the retinas of the monkeys fed the atherogenic diet. These results indicate that the single type of lipid alteration produced in the retina by a diet enriched in saturated fat and cholesterol is a decrease in the polyunsaturation of the retinal phospholipids. The reduction in retinal 22 : 6 content might have significance for photoreceptor function.

Animals↗
PubMedDate not supplied

Formation of a novel arachidonic acid metabolite in peroxisomes.

A new radiolabeled metabolite was released into the extracellular fluid by normal human skin fibroblasts that were labeled with [5,6,8,9,11,12,14,15-3H] arachidonic acid. This product continued to accumulate during a 24 h incubation, and its formation was not saturated at arachidonic acid concentrations up to 15 mumol/L. The compound, identified as hexadecatrienoic acid, was not produced by Zellweger fibroblasts which are deficient in peroxisomal fatty acid beta-oxidation. By contrast, radiolabeled hexadecatrienoic acid was produced by mutant fibroblasts having other peroxisomal defects, including X-linked adrenoleukodystrophy, adult Refsum's disease, and rhizomelic chondrodysplasia punctata. This radiolabeled metabolite also was produced by mutant fibroblasts that cannot oxidize long-chain fatty acids in the mitochondria. These results indicate that hexadecatrienoic acid is synthesized from arachidonic acid by peroxisomal beta-oxidation. The absence of this pathway may account for some of the biochemical and functional abnormalities that occur in Zellweger's syndrome.

Adrenoleukodystrophy↗
PubMedDate not supplied

Role of peroxisomal oxidation in the conversion of arachidonic acid to eicosatrienoic acid in human skin fibroblasts.

Human skin fibroblasts converted [5,6,8,9,11,12,14,15-3H]arachidonic acid ([3H]20:4) to eicosatrienoic acid (20:3), but appreciable amounts of radiolabeled 20:3 were not detected in corresponding incubations with [1-(14)C]20:4. This indicates that the main pathway for synthesizing 20:3 from arachidonic acid in the fibroblast involves oxidative removal of the carboxyl group of arachidonic acid. Fibroblasts deficient in long-chain acyl coenzyme A dehydrogenase (LCAD) converted [3H]20:4 to [3H]20:3. However, Zellweger fibroblasts that are deficient in peroxisomal fatty acid oxidation did not, indicating that the oxidative removal of the carboxyl group occurs in the peroxisomes. [3H]Hexadecatrienoic acid (16:3) was the main product that accumulated when [3H]20:4 was incubated with normal, LCAD deficient, and very long-chain acyl coenzyme A dehydrogenase (VLCAD) deficient fibroblasts, but Zellweger fibroblasts did not form this product. Normal fibroblasts converted [3H]16:3 to radiolabeled 20:3 and arachidonic acid. These findings suggest that some of the 16:3 produced from arachidonic acid by peroxisomal beta-oxidation can be recycled and that this recycling process constitutes a novel pathway for the conversion of arachidonic acid to 20:3 in human fibroblasts.

8,11,14-Eicosatrienoic Acid↗
PubMedDate not supplied

Comparison of 20-, 22-, and 24-carbon n-3 and n-6 polyunsaturated fatty acid utilization in differentiated rat brain astrocytes.

Astrocytes convert n-6 fatty acids primarily to arachidonic acid (20:4n-6), whereas n-3 fatty acids are converted to docosapentaenoic (22:5n-3) and docosahexaenoic (22:6n-3) acids. The utilization of 20-, 22- and 24-carbon n-3 and n-6 fatty acids was compared in differentiated rat astrocytes to determine the metabolic basis for this difference. The astrocytes retained 81% of the arachidonic acid ([(3)H]20:4n-6) uptake and retroconverted 57% of the docosatetraenoic acid ([3-(14)C]22:4n-6) uptake to 20:4n-6. By contrast, 68% of the eicosapentaenoic acid ([(3)H]20:5n-3) uptake was elongated, and only 9% of the [3-(14)C]22:5n-3 uptake was retroconverted to 20:5n-3. Both tetracosapentaenoic acid ([3-(14)C]24:5n-3) and tetracosatetraenoic acid ([3-(14)C]24:4n-6) were converted to docosahexaenoic acid (22:6n-3) and 22:5n-6, respectively. Therefore, the difference in the n-3 and n-6 fatty acid products formed is due primarily to differences in the utilization of their 20- and 22-carbon intermediates. This metabolic difference probably contributes to the preferential accumulation of docosahexaenoic acid in the brain.

Animals↗
PubMedDate not supplied

Elastic properties of the composite outer hair cell wall.

We propose a mathematical model for analyses of the elastic properties of the wall of the outer hair cell (OHC) in the inner ear. The model reflects the properties of the major components of the OHC wall: the subsurface cisternae, the cortical lattice, the plasma membrane, and the radial pillars. The wall is treated as a composite consisting of three elastic cylindrical shells. Two inner shells, isotropic and orthotropic/ are adjacent to each other, and the outermost isotropic shell is connected to the combined inner shell by elastic springs. We derive Flugge-type equations for the composite wall and apply the model to the interpretation of the experiments with axial loading and with inflation of the OHC. We derive expressions for the axial stiffness and the wall strains measured in these experiments in terms of the elastic properties of the wall components. We also consider a conceivable experiment with torsion of the OHC and obtain relations between the torque (the axial reaction) and the angle of torsion. These solutions provide necessary information for the future determination of the OHC elastic properties.

Biomechanical Phenomena↗
PubMedDate not supplied

Nonlinear electroelastic model for the composite outer hair cell wall.

A nonlinear electroelastic model for the composite wall of the cochlear outer hair cell is proposed. The cell wall is modeled as a two-layer shell with elastic connections between the layers: an active layer corresponds to the plasma membrane and a passive layer corresponds to a combination of the cytoskeleton and the subsurface cisternae. As a basis of the constitutive relations, a thermodynamic potential for such a composite wall is developed. Expressions for the components of the active force are obtained in terms of the active strains and the elastic properties of the passive and active layers. An application to the electrical stimulation of the cell under the conditions of the microchamber experiment is given. As a result, active strains, active forces, and mechanical energy stored in each of the two layers are presented as functions of the wall (membrane) potential.

Biomechanical Phenomena↗
PubMedDate not supplied

Linoleic acid metabolism and prostaglandin production by cultured bovine pulmonary artery endothelial cells.

When bovine pulmonary artery endothelial cells are cultured in a medium supplemented with linoleic acid, their capacity to produce prostacyclin (PGI2) is reduced by about 60%. This reduction occurs when PGI2 formation is stimulated by the addition of either the calcium ionophore A23187 or arachidonic acid. In addition, supplementation with linoleic acid reduced the production of prostaglandin E2 and F2 alpha from 1-14C-arachidonic acid by more than 50%. The capacity of cultured bovine pulmonary vein and aortic endothelial cells to convert extracellular arachidonic acid into PGI2 also was reduced by about 50% when the growth medium was supplemented with linoleic acid. Although bovine pulmonary artery endothelial cells incorporated large amounts of 1-14C-linoleic acid into cellular phospholipids and triglycerides, a maximum of only 2.3% of the radioactivity was converted to arachidonic acid in 24 hours. The most prevalent radioactive metabolite was eicosadienoic acid, the elongation product of linoleic acid. As compared with linoleic acid, the bovine endothelial cells incorporated 30% more 1-14C-arachidonic acid into phospholipids and 60% more into triglycerides. When the growth medium was supplemented with linoleic acid, the percentage of this fatty acid in cellular lipids increased 3- to 4.5-fold and eicosadienoic acid accumulated, accounting for up to 9% of the cellular fatty acids. This increase was accompanied by a 30% to 45% reduction in arachidonic acid. These findings, together with our previous results with human umbilical vein endothelium, suggest that an inability to convert large amounts of linoleic to arachidonic acid and a suppressive effect of linoleic acid enrichment on prostaglandin production may be general properties of endothelial cells.

Animals↗
PubMedDate not supplied

Dietary fat saturation and hepatic acylcoenzyme A:cholesterol acyltransferase activity. Effect of n-3 polyunsaturated and long-chain saturated fat.

The acylcoenzyme A:cholesterol acyltransferase (ACAT) activity in liver microsomes from rats fed a diet containing 14% menhaden oil (Mp) for 11 days was 117% higher than that in microsomes from rats fed a corresponding diet containing 14% cocoa butter (Ms). There were no differences in the cholesterol and phospholipid contents of Mp and Ms or in the activities of palmitoyl coenzyme A hydrolase and NADPH cytochrome c reductase. NADPH-dependent lipid peroxidation was higher in Mp, whereas glucose 6-phosphatase activity was higher in Ms. These findings indicate that the ACAT response to differences in dietary fat saturation is not due to a nonspecific effect of these diets on microsomal enzymes. When 1% cholesterol was added to the diets, the cholesterol content and ACAT activity of both microsomal preparations increased, but the ACAT activity of Mp remained 60% higher than that of Ms. Addition of cholesterol by incubation of the microsomes with liposomes also increased ACAT activity. At corresponding cholesterol contents, however, the ACAT activity of Mp remained 50% to 70% above that of Ms. There was no difference in the plasma cholesterol concentration in the two groups of rats, indicating that the ACAT effect probably is not due to a difference in the amount of circulating cholesterol available to the liver. Mp contained 40% more polyunsaturated fatty acids and five times more n-3 polyunsaturates than Ms. These findings suggest that the increase in ACAT activity in Mp is due, at least in part, to the difference in the fatty acid composition of the microsomes.

Acyltransferases↗
PubMedDate not supplied

Arachidonic acid availability and prostacyclin production by cultured human endothelial cells.

When human umbilical vein endothelial cultures were grown in the presence of supplemental arachidonic acid, the cell phospholipids became enriched with arachidonic acid. Prostacyclin (PGI2) accumulated in the medium during supplementation with arachidonic acid. The capacity of these enriched cultures to produce PGI2 when subsequently incubated with either arachidonic acid or thrombin was reduced by as much as 90%, but release of arachidonic acid from the cell lipids in response to thrombin stimulation was not inhibited. Refractory cultures completely recovered the capacity to form PGI2 within 18 hours after removal of the medium containing supplemental arachidonic acid. However, recovery was prevented by cycloheximide. When enrichment with arachidonic acid was done in the presence of ibuprofen, a reversible cyclooxygenase inhibitor, PGI2 did not accumulate in the medium during supplementation, and the subsequent capacity of the cultures to produce PGI2 in response to thrombin increased by 70% to 240%. By contrast, the capacity of these supplemented cultures to convert added arachidonic acid to PGI2 did not increase. Therefore, the enhancement in thrombin-stimulated PGI2 production when the cultures are supplemented with arachidonic acid probably is due to the larger amount of arachidonic acid available in the intracellular lipid substrate pools, rather than to an activation of the PGI2 synthetic pathway. These findings suggest that changes in the arachidonic acid content of the endothelial cell lipids may modulate the capacity of the endothelium to produce PGI2 in response to stimulation.

Arachidonic Acid↗
PubMedDate not supplied

Exposure to free fatty acid increases the transfer of albumin across cultured endothelial monolayers.

An initial exposure to high concentrations of free fatty acid increased the transfer of albumin across cultured endothelial monolayers. The rate and amount of albumin transfer was dependent on the oleic acid concentration to which the cultures were initially exposed, with 300 microM producing the maximum transfer. The albumin transfer also increased with the increasing time of exposure to oleic acid, the maximum effect occurring during the first 24 hours. An exposure to 300 microM linoleic acid produced an even greater increase in albumin transfer than did 300 microM oleic acid. The increased albumin transfer observed when cells were exposed to high concentrations of free fatty acid was largely reversible after reincubation of the cell monolayers in free fatty acid-poor media. In parallel experiments, radioactive oleic acid incorporation into cell triglycerides increased linearly as the fatty acid concentration was raised, with cell triglyceride content increasing up to sevenfold after incubation in a medium containing 300 microM oleic acid. A significant amount of oleic acid was incorporated into phospholipids, and the fatty acid composition of the endothelial triglycerides and phospholipids was modified. All these effects of oleic occurred without altering the incorporation of leucine into the cell protein. These results indicate that exposure to high concentrations of free fatty acid can alter endothelial cell lipid composition, and that this increases the albumin transfer across endothelium. This process might permit more macromolecules to enter the arterial wall.

Albumins↗
PubMedDate not supplied

Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain.

Polyunsaturated fatty acids (PUFA), which comprise 25-30% of the fatty acids in the human brain, are necessary for normal brain development and function. PUFA cannot be synthesized de novo and must be supplied to the brain by the plasma. It is necessary to know the PUFA content and composition of the various plasma lipids and lipoproteins in order to understand how these fatty acids are taken up and metabolized by the brain. Human plasma free fatty acid (FFA) ordinarily contains about 15% linoleic acid (18:2n-6) and 1% arachidonic acid (AA) (20:4n-6). Plasma triglycerides, phospholipids, and cholesterol esters also are rich in linoleic acid, and the phospholipids and cholesterol esters contain about 10% AA. These findings suggest that the brain probably can obtain an adequate supply of n-6 PUFA from either the plasma FFA or lipoproteins. By contrast, the plasma ordinarily contains only one-tenth as much n-3 PUFA, and the amounts range from 1% alpha-linolenic acid (18:3n-3) in the plasma FFA to 2% docosahexaenoic acid (22:6n-3, DHA) in the plasma phospholipids. The main n-3 PUFA in the brain is DHA. Therefore, if the plasma FFA is the primary source of fatty acid for the brain, much of the DHA must be synthesized in the brain from n-3 PUFA precursors. Alternatively, if the brain requires large amounts of preformed DHA, the phospholipids contained in plasma lipoproteins are the most likely source.

Animals↗
PubMedDate not supplied

Brain uptake and utilization of fatty acids: recommendations for future research.

A primary goal of the international workshop "Brain Uptake and Utilization of Fatty Acids" was to identify research areas that would benefit from further investigation. The major themes for future research are presented below: (1) Elucidating the role of the developing and mature cerebrovascular endothelium (CVE) in the uptake of fatty acids (FA) into the brain. (2) Clarifying the role of diffusion and receptor-mediated uptake of FAs by various brain cell membranes and protein-mediated shuttling of FAs between the CVE and various brain cells and tissues. (3) Illuminating the mechanisms of intermediate metabolism and the roles of polyunsaturated fatty acids (PUFA) in astrocytes, neurons and oligodendrocytes. Of special interest are the long-chain omega-3 PUFA and their derivatives, such as lipoproteins, phospholipids and plasmalogens, that have been associated with various disease states (such as those listed in [5], below). (4) Elucidating the role of gene expression on long-chain omega-3 PUFA incorporation in membranes and the regulatory role these and other PUFA have on gene expression in the brain. (5) Elucidating the recently identified roles of long-chain omega-3 PUFA in mood disorders, schizophrenia, stroke, peroxisomal biogenesis disorders, Huntington's disease, other neurodegenerative disorders and disorders of oxidative stress. (6) Undertaking placebo-controlled clinical trials to assess the therapeutic potential of omega-3 PUFA in the above disorders. (7) Developing new, and utilizing existing animal models in the above studies. (8) Developing noninvasive imaging and tagging methods for quantifying the migration and distribution of PUFA and their derivatives in the brain. (9) Applying multi-disciplinary collaborations among biophysicists, physiologists and molecular biologists to the resolution of the above.

Animals↗
PubMedDate not supplied

Brain uptake and utilization of fatty acids: applications to peroxisomal biogenesis diseases.

The brain is rich in diverse fatty acids saturated, monounsaturated and polyunsaturated fatty acids with chain lengths ranging from less than 16 to more than 24 carbons that make up the complex lipids present in this organ. While some fatty acids are derived from endogenous synthesis, others must come from exogenous sources. The mechanism(s) by which fatty acids enter cells has been the subject of much debate. While some investigators argue for a protein-mediated process, others suggest that simple diffusion is sufficient. In the brain, uptake is further complicated by the presence of the blood-brain barrier. Brain fatty acid homeostasis is disturbed in many human disorders, as typified by the peroxisomal biogenesis diseases. A workshop designed to bring together researchers from varied backgrounds to discuss these issues in an open forum was held in March, 2000. In addition to assessing the current state of knowledge, areas requiring additional investigation were identified and recommendations for future research were made. A brief overview of the invited talks is presented here.

Animals↗