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Biomedical subjects

J S Charnock

Publications and source records attributed to J S Charnock.

At least 55 records · Page 3Linked to original sources
PubMed1985

Changes in fatty acid composition of the cardiac phospholipids of the cotton-eared marmoset (Callithrix jacchus) after feeding different lipid supplements.

After feeding marmosets different lipid supplements for 6 months, the distribution of phospholipid classes and the fatty acid composition of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidylglycerol (DPG) were determined in their cardiac membranes. Supplementing the diet with linoleic-acid-rich sunflower seed oil raised the level of 18:2,n-6 in both PC and PE, but did not change the level significantly in DPG. When 18:2,n-6 was increased, the level of arachidonic acid (20:4,n-6) was significantly decreased in PC and PE. No arachidonic acid was present in DPG. Supplementing the diet with mutton fat did not markedly increase the level of saturated fats, nor did it markedly reduce the level of arachidonic acid in any phospholipid component. No dietary treatment altered the distribution of the major phospholipid classes.

Animals↗
PubMed1985

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid.

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.

Adipose Tissue↗
PubMed1985

Diet and cardiac arrhythmia: effects of lipids on age-related changes in myocardial function in the rat.

Male rats were fed for 3-4 months (short-term) or 12-15 months (long-term) on a standard laboratory diet alone (control) or supplemented with sunflower seed oil (SSO, 12% w/w) or sheep kidney fat (SKF, 12% w/w). Papillary muscles were electrically driven (1 Hz, 5 ms, supramaximal voltage) at 37 degrees C in Krebs-Henseleit solution, and contractions were measured isometrically. Both the positive inotropic responses to CA++ and the incidence of spontaneous tachyarrhythmias under catecholamine stress were increased by short-term SKF feeding and with age in control and SKF groups, whereas SSO prevented these changes. The results show a marked effect of age upon ventricular myocardial function in the rat, which appears to be accelerated by the consumption of animal (saturated) fat while polyunsaturated vegetable oil provides some degree of protection. It is suggested that changes in membrane lipid composition can alter the Ca++ handling characteristics of myocardial cells.

Age Factors↗
PubMed1984

Species variation in the ouabain sensitivity of cardiac Na+/K+-ATPase. A possible role for membrane lipids.

The role of membrane lipid composition on the modulation of ouabain sensitivity of cardiac Na+/K+-ATPase has been studied in vitro using several animal species. The animals can be grouped as ouabain-sensitive and ouabain-insensitive species. Ouabain-sensitive species (I50; 0.5-2.2 microM) include sheep, marmoset, pig and the guinea pig, whilst rat and mouse form the ouabain-insensitive group (I50; 100-105 microM). Although no species variation in the distribution of major phospholipid classes was observed, significant differences were apparent in the proportions of certain saturated and unsaturated phospholipid fatty acids. Thus, there was a marked increase in the relative proportion of docosahexaenoic (22:6, omega-3) acid in the Na+/K+-ATPase preparations from the rat and mouse compared to ouabain-sensitive species. Despite these differences, all animals had similar proportions of total saturated (sigma SAT) and total unsaturated (sigma Unsat) fatty acids. On the other hand, a good correlation between the unsaturation index of membrane lipids and I50 value for ouabain was observed. It is proposed that acyl chain characteristics (unsaturation and/or chain length) rather than the head group of the phospholipid molecule play a major role in the modulation of Na+/K+-ATPase to inhibition by ouabain.

Animals↗
PubMed1984

Response of rat heart membranes and associated ion-transporting ATPases to dietary lipid.

The effects of different dietary fat intake on the lipid composition and enzyme behaviour of sarcolemmal (Na+ + K+)ATPase and sarcoplasmic reticulum Ca2+-ATPase from rat heart were investigated. Rat diets were supplemented with either sunflower seed oil (unsatd./satd. 5.6) or sheep kidney fat (unsatd./satd. 0.8). Significant changes in the phospholipid fatty acid composition were observed in both membranes after 9 weeks dietary lipid treatment. For both membranes, the total saturated/unsaturated fatty acid levels were unaffected by the dietary lipid treatment, however the proportions of the major unsaturated fatty acids were altered. Animals fed the sunflower seed oil diet exhibited an increase in n-6 fatty acids, including linoleic (18:2(n-6] and arachidonic (20:4(n-6] while the sheep kidney fat dietary rats were higher in n-3 fatty acids, principally docosahexaenoic (22:6), with the net result being a higher n-6/n-3 ratio in the sunflower seed oil group compared to sheep kidney fat dietary animals. Fluorescence polarization indicated that the fluidity of sarcoplasmic reticular membrane was greater than that of sarcolemmal membrane, with a dietary lipid-induced decrease in fluidity being observed in the sarcoplasmic reticular membrane from sheep kidney fat dietary animals. Despite these significant changes in membrane composition and physical properties, neither the specific activity nor the temperature-activity relationship (Arrhenius profile) of the associated ATPases were altered. These results suggest that with regard to the parameters measured in this study, the two ion-transporting ATPases are not modulated by changes which occur in the membrane lipid composition as a result of the diet.

Animals↗
PubMed1984

Homeostatic control of membrane fatty acid composition in the rat after dietary lipid treatment.

Diets in which both the lipid content and composition (polyunsaturated to saturated fatty acid ratio) were varied were fed to rats for 20 weeks, and the effects on the tissue lipid profiles were determined. The fatty acid profile of the plasma lipids, and the phospholipid fatty acids of the mitochondrial and microsomal fractions of liver, heart, kidney and brain, as well as erythrocyte membranes were determined. Despite large differences in the level and type of lipid present in the experimental diets and in the proportion of saturated fatty acids in the plasma lipids in response to the various diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the various membranes examined. The major effect of altering the dietary level of polyunsaturated to saturated fatty acids was on the ratio of the omega 6/omega 3 series of unsaturated fatty acids in the membrane lipids. This change occurred in all tissues except the brain, in which only a small response to altered dietary lipid intake was observed. The omega 6/omega 3 ratio was elevated upon feeding a diet rich in omega 6 polyunsaturated fatty acids, but decreased when a diet rich in saturated fatty acids was fed. The failure to significantly alter membrane lipid saturation/unsaturation in the tissues examined would suggest that a homeostatic mechanism is operative in biological membranes and may act to buffer membranes from the effects of changes in the nature of the dietary lipid intake.

Animals↗
PubMed1984

The composition of cardiac phospholipids in rats fed different lipid supplements.

Changes in dietary lipid intake are known to alter the fatty acid composition of cardiac muscle of various animals. Because changes in cardiac muscle membrane structure and function may be involved in the pathogenesis of arrhythmia and ischemia, we have examined the effects of dietary lipid supplements on the phospholipid distribution and fatty acid composition of rat atria and ventricle following 20 weeks feeding of diets supplemented with either 12% sunflower-seed oil or sheep fat. Neither lipid supplement produced significant changes in the proportions of cholesterol, total phospholipids or phosphatidylcholine, phosphatidylethanolamine or diphosphatidylglycerol,--the phospholipid classes that together account for more than 90% of the total phospholipids of rat cardiac muscle. Significant changes were found in the profiles of the unsaturated fatty acids of all 3 phospholipid components of both atria and ventricle. Although similar, the changes between these tissues were not identical. However, in general, feeding a linoleic acid-rich sunflower seed oil supplement resulted in an increase in the omega-6 family of fatty acids, whereas feeding the relatively linoleic acid-poor sheep fat supplement decreased the level of omega-6 fatty acids but increased the levels of the omega-3 family, resulting in major shifts in the proportions of these families of acids. In particular, the ratio of arachidonic acid: docosahexaenoic acid (20:4,omega-6/22:6,omega-3), which is higher in all phospholipids of atria than ventricle, is increased by feeding linoleic acid, primarily by increasing the level of arachidonic acid in the muscle membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

A comparison of mitochondrial respiration and membrane lipid composition in the rat and marmoset following dietary lipid supplementation.

Rats and marmosets were fed different lipid supplemented diets and the phospholipid fatty acid composition and the respiration rate of liver and heart mitochondria were determined. For both species, diets of differing lipid saturation had little effect on the ratio of saturated to unsaturated fatty acids in the mitochondrial membranes, however the omega 6/omega 3 unsaturated fatty acid ratio was significantly altered by diets of different lipid saturation. In comparison to animals fed low fat diets, mitochondrial respiration in the marmoset was reduced by high fat diets irrespective of the dietary level of lipid saturation. This effect of high fat diets on mitochondrial respiration was not observed for the rat.

Animals↗
PubMed1983

Differential modulation of rat heart mitochondrial membrane-associated enzymes by dietary lipid.

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflower seed oil were fed to rats and the effect on heart mitochondrial lipid composition and membrane-associated enzyme behaviour was determined. The dietary lipid treatments did not change the overall level of membrane lipid unsaturation but did alter the proportion of various unsaturated fatty acids. This led to a change in the omega 6/omega 3 unsaturated fatty acid ratio, which was highest in the sunflower seed oil fed rats. Arrhenius plots of the mitochondrial membrane associated enzymes succinate-cytochrome c reductase and oligomycin-sensitive adenosinetriphosphatase (ATPase) after dietary lipid treatment revealed different responses in their critical temperature. For succinate-cytochrome c reductase, the critical temperature was 29 degrees C for rats fed the sheep kidney fat diet and 20 degrees C for rats fed the sunflower seed oil diet. In contrast, no shift in the critical temperature for the mitochondrial ATPase was apparent as a result of the differing dietary lipid treatments. The results suggest that the discontinuity in the Arrhenius plot of succinate-cytochrome c reductase is induced by some change in the physical properties of the membrane lipids. In contrast, mitochondrial ATPase appears insensitive, in terms of its thermal behaviour, to changes occurring in the composition of the membrane lipids. However, the specific activity of the mitochondrial ATPase was affected by the dietary lipid treatment being highest for the rats fed the sheep kidney fat diet. No dietary lipid effect was observed for the specific activity of succinate-cytochrome c reductase. This differential response of the two mitochondrial membrane enzymes to dietary-induced changes in membrane lipid composition may affect mitochondrial oxidative phosphorylation.

Adenosine Triphosphatases↗
PubMed1983

The effect of dietary lipids on the thermotropic behaviour of rat liver and heart mitochondrial membrane lipids.

Diets supplemented with relatively high levels of either saturated fatty acids derived from sheep kidney fat (sheep kidney fat diet) or unsaturated fatty acids derived from sunflower seed oil (sunflower seed oil diet) were fed to rats for a period of 16 weeks and changes in the thermotropic behaviour of liver and heart mitochondrial lipids were determined by differential scanning calorimetry (DSC). The diets induced similar changes in the fatty acid composition in both liver and heart mitochondrial lipids, the major change being the omega 6 to omega 3 unsaturated fatty acid ratio, which was elevated in mitochondria from animals on the sunflower seed oil diet and lowered with the mitochondria from the sheep kidney fat dietary animals. When examined by DSC, aqueous buffer dispersions of liver and heart mitochondrial lipids exhibited two independent, reversible phase transitions and in some instances a third highly unstable transition. The dietary lipid treatments had their major effect of the temperature at which the lower phase transition occurred, there being an inverse relationship between the transition temperature and the omega 6 to omega 3 unsaturated fatty acid ratio. No significant effect was observed for the temperature of the higher phase transition. These results indicate that certain domains of mitochondrial lipids, probably containing some relatively higher melting-point lipids, independently undergo formation of the solidus or gel phase and this phenomenon is not greatly influenced by the lipid composition of the mitochondrial membranes. Conversely, other domains, representing the bulk of the membrane lipids and which probably contain the relatively lower melting point lipids, undergo solidus phase formation at temperatures which reflect changes in the membrane lipid composition which are in turn, a reflection of the nature of the dietary lipid intake. These lipid phase transitions do not appear to correlate directly with those events considered responsible for the altered Arrhenius kinetics of various mitochondrial membrane-associated enzymes.

Animals↗
PubMed1983

Lipid-protein interactions of reconstituted membrane-associated adenosinetriphosphatases. Use of a gel-filtration procedure to examine phospholipid-activity relationships.

A gel-filtration procedure is described for the reconstitution of partially delipidated membrane adenosinetriphosphatases (Mg2+-ATPase and (Na+ + K+)-ATPase) into liposomes of defined composition. After detergent solubilization of membrane enzyme preparations, reconstitution of these ATPases was achieved by the rapid removal of deoxycholate by Sephadex G-50 chromatography. Proteoliposomes were separated from unincorporated enzyme by chromatography on Sepharose CL-4B. Sedimentation characteristics in sucrose density gradients and electron microscopy confirmed that both Mg2+-ATPase and (Na+ + K+)-ATPase were reconstituted into liposomes of phosphatidylcholine and yielded preparations having high recoveries of enzyme activity by comparison with the control membrane preparations. Reconstitution of (Na+ + K+)-ATPase into synthetic phosphatidylcholines of defined fatty acid composition reveals an inverse relationship between enzyme activity and the chain length of the saturated fatty acids DMPC, DPPC and DSPC. Higher recoveries were obtained when one or more fatty acid chains was unsaturated. Full reactivation occurred with DOPC (18:1/18:1). There was a positive correlation between the specific activity of reconstituted (Na+ + K+)-ATPase and the temperature of the thermal phase transition of the synthetic phosphatidyl cholines studied. This was not seen with Mg2+-ATPase. It is suggested that 'membrane fluidity' influences the catalytic activity of (Na+ + K+)-ATPase but not that of Mg2+-ATPase.

Adenosine Triphosphatases↗
PubMed1983

Modulation of cardiac glycoside inhibition of (Na+ + K+)-ATPase by membrane lipids. Difference between species.

The role of lipids in the modulation of the ouabain-sensitivity of membrane (Na+ + K+)-ATPase from different species has been studied using a reconstitution procedure which promotes lipid exchange during detergent depletion by Sephadex chromatography. Hybrid reconstitution of delipidated (Na+ + K+)-ATPase preparations from bovine brain into the lipids obtained from crab nerve enzyme preparations significantly reduces the sensitivity of the brain enzyme to inhibition by ouabain. Conversely, reconstitution of crab nerve enzyme into the lipids from bovine brain enzyme preparations increases the sensitivity of the crab enzyme to ouabain inhibition. These opposing effects demonstrate the role of membrane lipids in modulating the enzyme-inhibition relationship in preparations from these different species.

Animals↗
PubMed1983

Dietary lipid modulation of rat liver mitochondrial succinate: cytochrome c reductase.

Diets supplemented with high levels of either saturated fatty acids or unsaturated fatty acids were fed to adult rats for a period of 9 weeks and changes in the liver mitochondrial membrane phospholipid fatty acid composition and thermal behaviour of succinate: cytochrome c reductase were determined. The dietary treatment induced a change in the omega 6 to omega 3 unsaturated fatty acid ratio in the membrane lipids, with the ratio being highest with the unsaturated fatty acid and lowest with the saturated fatty acid diet. Arrhenius plots of succinate: cytochrome c reductase activity exhibited differences in both critical temperature (Tf) and Arrhenius activation energy (Ea) depending on the type of dietary treatment. The Tf was elevated from 23 degrees C in control to 32 degrees C in the saturated fatty acid-supplemented group. No significant effect on the Tf was observed in the unsaturated fatty acid-supplemented group however higher Ea values were observed due to the unsaturated fatty acid diet. The changes in succinate: cytochrome c reductase are probably due to changes in the lipid-protein interactions in the membrane, induced by the dietary lipid supplementation.

Animals↗
PubMed1983

Differences in the fatty acid composition of atrial and ventricular phospholipids of rat heart following standard and lipid-supplemented diets.

1. The major saturated fatty acids of the phospholipids of rat heart atria and ventricles are similar and are not greatly altered by supplementing the diet with widely different types of lipid. 2. There are important differences in the relative proportions of the major unsaturated fatty acids of the phospholipids of these anatomically and functionally distinct regions of the heart. 3. The proportions of linoleic (C18:2, eta-6) and docosahexaenoic (C22:6, eta-3) acid are significantly higher in the ventricles than in the atria; the proportions of oleic (C18:1, eta-9) arachidonic (C20:4, eta-6) and docosatetraenoic acids (22:4, eta-6) are higher in atria. 4. The differences in unsaturated fatty acid profiles persist even after twelve months of feeding lipid supplements of sunflower seed oil (SSO) or sheep kidney (perirenal) fat (SKF). 5. However, the ratios of arachidonic to docosahexaenoic acid in both tissues are changed by decreasing the intake of linoleic acid, which apparently favours the conversion of dietary linolenic (C18:3, eta-3) to docosahexaenoic acid. The level of docosahexaenoic acid is greater in the ventricles than in the atria, and greatest when the animals were fed SKF diet. 6. The physiological and pharmacological differences in ventricles and atria may arise from differences as fundamental as the phospholipid fatty acid composition of cardiac membranes.

Animals↗
PubMed1983

Seasonal variations in drug response and staircase phenomena in atrial muscle from a hibernating rodent (Spermophilus richardsonii).

1 Electrically driven atrial muscle from a hibernating rodent (Spermophilus richardsonii) showed marked seasonal variations in inotropic responsiveness to both the cardiac glycoside actodigin and to raised extracellular calcium concentration. In contrast, glycoside toxicity was apparent and comparable in all tissues. 2 These variations were accompanied by changes in force-frequency ('staircase') characteristics of the tissues. 3 In contrast, no seasonal variation was observed in either positive inotropic responses to rubidium (a non-glycoside inhibitor of Na+ + K+ ATP-ase) or negative inotropic responses to methacholine. 4 In summer atria the calcium antagonist, verapamil (6 x 10(-7) M) abolished the positive staircase phenomenon but did not modify the positive inotropic actions of actodigin. 5 These data do not support the hypothesis that 'staircase' and glycoside-induced inotropism are mediated through a common mechanism.

Animals↗
PubMed1983

Gated blood-pool studies of cardiac function in the rat and marmoset.

To develop a sensitive, relatively noninvasive method for monitoring cardiac function in small laboratory animals, equilibrium gated blood-pool imaging (with Tc-99m RBC) was adapted for use in an inbred strain of laboratory rats of 400-470 g body weight and in marmosets of 320-400 g body weight. A 2-mm pinhole collimator was fitted to the gamma camera to produce a distinct image of the left ventricle following intravenous injection of 5 mCi of pertechnetate. Reproducible and consistent data for heart rate, left-ventricular ejection fraction, and peak ejection rate were obtained from studies on 13 male rats and five marmosets maintained on constant diets. An intravenous injection of 0.4 microgram of isoprenaline led to predictable increases in heart rate, left-ventricular ejection fraction, and peak ejection rate, and provided evidence of the sensitivity of the method in monitoring heart function in small laboratory animals.

Animals↗