Biomedical subjects

G Y Sun

Publications and source records attributed to G Y Sun.

At least 109 records · Page 6Linked to original sources

PubMed1988

Alterations in rat brain polyphosphoinositide metabolism due to acute ethanol administration.

The effects of acute ethanol administration on the polyphosphoinositide metabolism of rat brain cerebral cortex were examined. Intracerebral injections of [gamma-32P]ATP proved to be an effective in vivo method to prelabel brain phospholipids, especially the polyphosphoinositides. High acute doses of ethanol (8 or 6 g/kg b.wt.) administered by gavage significantly inhibited the breakdown of polyphosphoinositides as judged by an elevation in the concentration as well as the labeling of these compounds. Concomitantly, there was a significant reduction in the level of diacylglycerols. Low acute doses of ethanol (2 g/kg b.wt.) did not seem to have any effects on the basal levels or labeling of these compounds. The changes in polyphosphoinositide labeling due to ethanol intoxication were reverted to near control values when animals regained their righting reflex (approximately 4 hr). These studies demonstrate that, under normal conditions, polyphosphoinositides and diacylglycerols are maintained in a dynamic equilibrium and that acute doses of ethanol can suppress the signal transduction process and disturb this equilibrium.

Adenosine Triphosphate↗

PubMed1987

Purification of long-chain acyl-CoA hydrolase from bovine heart microsomes and regulation of activity by lysophospholipids.

Long-chain acyl-CoA hydrolase (EC 3.1.2.2) has been purified 12,000-fold from bovine heart muscle microsomes by extraction with Miranol detergent, followed by column chromatography on Reactive Blue agarose and DEAE-cellulose. The purified enzyme was nearly homogeneous on polyacrylamide gel electrophoresis and had a molecular weight of 41,000 in the presence of dodecyl sulfate. The specificity and kinetic properties of the enzyme were studied using several acyl-CoA derivatives as potential substrates. The enzyme showed a wide degree of specificity with little dependence on either the fatty acyl chain length or the degree of unsaturation of the acyl group. The kinetic properties were in accord with the Michaelis-Menten equation under most conditions, although high concentrations of substrates generally inhibited the enzyme. Arachidonoyl-CoA, which was the most effective substrate, had a Km value of 0.4 microM and a Vmax value of 6.0 mumol min-1 mg-1. The enzyme was strongly and specifically inhibited by constants of 16 and 30 nM, respectively. Other lysolipids and detergents such as deoxycholate and Triton X-100 were weak inhibitors. These properties and others distinguish this enzyme from other acyl-CoA hydrolases and support the idea that lysophospholipids may be important in vivo in the regulation of lipid metabolism.

Animals↗

PubMed1987

An initial screening of serum lipids and fatty acid profiles of hypertensive and normotensive subjects.

Serum lipids and their acyl group profiles from a group of hypertensive patients with elevated systolic and diastolic pressure were compared with normotensive subjects of matched age, body weight and dietary habits. The level of serum triacylglycerols was elevated in the hypertensive subjects, but the cholesterol level remained normal. The acyl groups of serum triacylglycerols and cholesterylesters from hypertensive subjects indicated a higher proportion of the saturated fatty acids (16:0 and 18:0) and a lower proportion of linoleic acid (18:2) as compared to normal controls. There was no obvious change in the level and acyl group composition of serum phosphatidylcholine between the two groups. Since the hypertensive and normotensive subjects indicated similar dietary habits, the resulting differences in serum lipids reflected an abnormality in the lipolytic process in the hypertensive subjects.

Body Weight↗

PubMed1987

Acidic phospholipids, diacylglycerols, and free fatty acids in gerbil brain: a comparison of ischemic changes resulting from carotid ligation and decapitation.

The levels of brain acidic phospholipids (poly-PI, PI, PA, and PS), DG, and FFA and their acyl group profiles were determined after induction of ischemia in gerbils by ligation of the common carotid arteries and decapitation. Ischemia induced by both procedures resulted in a significant decrease in poly-PI (20% for 1-min decapitation and 1-min ligation). Except for a 16% increase in PI in the 5-min decapitation group, no apparent change was found in other phospholipids after either ischemic condition. The level of DG was increased one- and three-fold after 1 and 5 min, respectively, of decapitative ischemic treatment. Ligation of the carotid arteries for 1 min resulted also in a one-fold increase in the DG level. The decapitative model resulted in a one- and five-fold increase in FFA level (with respect to 1 and 5 min, respectively), whereas ligation for 1 min resulted in an increase of 42% of the FFA. The acyl groups of poly-PI and PI in the control gerbil brain are enriched in 18:0 and 20:4, but those of DG, FFA, and PA have a higher proportion of 16:0 besides 18:0 and 20:4. However, a preferential increase in the proportion of 18:0 and 20:4 was shown for the DG and FFA in both types of ischemic treatments. It is concluded from the results that both models of ischemic treatment elicit a similar decrease in poly-PI and increase in DG, but differ in the amount of FFA release. The higher level of FFA release in the decapitative model suggests that other biochemical mechanisms may be activated to cause the additional release.

Animals↗

PubMed1987

Lysophospholipase activity in rat brain subcellular fractions.

Lysophospholipase activity in brain subcellular fractions was measured by the release of myristic acid from 1-myristoylglycerophosphocholine or through the formation of [32P]glycerophosphocholine from [32P]lysophosphatidylcholine. Although the lysophospholipase activity was highest in microsomes, considerable enzyme activity was also found in other subcellular membrane fractions. The pH optimum for the microsomal enzyme was around 7, whereas the synaptosomes and non-synaptic plasma membranes exhibited a pH maximum around 8. Although the enzyme did not require divalent cations for activity, divalent cations (1 mM) such as Hg2+, Cu2+, and Zn2+ inhibited potently the enzyme activity. Enzyme activity was also partially inhibited by both saturated and polyunsaturated fatty acids (25-200 microM), and the inhibition seemed to be greater in the membrane than in the cytosolic fractions. Ionic detergents such as deoxycholate and taurocholate inhibited the lysophospholipase. On the other hand, the effect of Triton X-100 was biphasic, i.e., stimulation at concentrations below 100 micrograms/mg protein and inhibition at higher concentrations. Addition of cholesterol (50-250 micrograms/ml), but not cholesteryl esters, also potently inhibited enzyme activity. The presence of active lysophospholipase(s) in brain is probably an important mechanism for preventing unnecessary accumulation of lysophospholipids which may exert a deleterious effect on the membranes because of their detergent properties.

Animals↗

PubMed1987

Effects of cerebral ischemia on [3H]inositol lipids and [3H]inositol phosphates of gerbil brain and subcellular fractions.

Intracerebral injection of [3H]inositol into gerbil brain resulted in labeling of phosphoinositides and inositol-phosphates in various subcellular membrane fractions. Phosphatidylinositol (PI) comprised greater than 90% of the radioactivity of inositol lipids. However, the level of labeled poly-PI (with respect to PI) was higher in synaptosomes than in other membrane fractions. Ischemia induced in gerbils by ligation of the common carotid arteries resulted in a 30% decrease in labeled poly-PI in brain homogenates and this decrease was largely attributed to the poly-PI in synaptosomes (50% decrease). Among the inositol phosphates, the ischemia induction resulted in a decrease in labeling of inositol triphosphate (63%) and inositol biphosphate (38%), but labeling of inositol phosphate (IP) was increased by 59%. The results suggested a rapid turnover of the inositol phosphates in the gerbil brain. In general, changes in inositol lipids and inositol phosphates due to ischemia were attenuated after pretreatment with lithium (3 meq/kg) injected intraperitoneally 5 h prior to ligation. Surprisingly, lithium treatment alone did not cause an increase in IP labeling in the gerbil brain.

Animals↗

PubMed1987

Effects of chronic ethanol administration on rat brain phospholipid metabolism.

Alterations in brain phospholipid metabolism were observed after chronic ethanol administration for 16 days to developing rats. Animals were injected intraperitoneally with 32Pi 16 h prior to killing. Overall uptake of 32Pi by brain did not differ between the control and ethanol-treated groups, which were killed 2 h and 24 h after the last ethanol feeding. Except for an increase in the labeling of myelin after ethanol treatment, the amount of radioactivity recovered in the synaptosomal-mitochondrial and plasma membrane fractions of control and ethanol-treated groups was not different. Relative to the radioactivity of phosphatidylcholines, which indicated no change, there were increases (20-44%) in labeling of ethanolamine plasmalogens, phosphatidic acids, and phosphatidylinositols in cortical synaptosomes from the 2-h ethanol-treated group. In the plasma membrane fractions, however, increases (9-14%) in labeling of phosphatidylserines and phosphatidylinositols were observed in both 2- and 24-h ethanol-treated groups. In both membrane fractions, there was an obvious increase (44-86%) in labeling of polyphosphoinositides at 24 h after withdrawal from ethanol. Results thus indicate an adaptive increase in the biosynthesis of ethanolamine plasmalogen and brain acidic phospholipids due to chronic ethanol administration. Furthermore, the increase in labeling of polyphosphoinositides in the 24-h withdrawal group may reflect the hypoactivity associated with ethanol withdrawal.

Animals↗

PubMed1987

Ethanol effects on phospholipids and triacylglycerols of rat brain astrocyte cell line.

A homotypic population of rat brain astrocyte (RBA-1) cell line was used to investigate the effects of ethanol on uptake of [3H]-arachidonic acid and incorporation of label into phospholipids and neutral lipids in the cell. Incubation of the cells with [3H]-arachidonic acid resulted in labeling of most phospholipids and triacylglycerols, although individual phospholipids exhibited different rates for acquiring the label. Labeled arachidonate was first incorporated into phosphatidylcholines and phosphatidylinositols prior to equilibriation with other phospholipids. In short term incubation (8 hr), ethanol (128-255 mM) enhanced the incorporation of labeled arachidonate into most phospholipids. In addition, ethanol at 128 mM enhanced the labeling of the triacylglycerols, and the difference was greater with increasing time of ethanol exposure. It is concluded that ethanol enhanced the uptake and incorporation of polyunsaturated fatty acids into the cell membrane lipids. This study further indicates the feasibility of using the RBA-1 cells in culture to probe the effects of ethanol on membrane lipid metabolism.

Animals↗

PubMed1987

Effects of ethanol on acetylcholine and GABA release: differences in the role of potassium.

Ethanol inhibited electrically stimulated [3H]ACh release from cortical brain slices, but not when release was stimulated by high potassium. In contrast, ethanol was ineffective on electrically stimulated release of [14]GABA from cortical brain slices, but inhibited potassium-induced release. Ethanol also significantly inhibited potassium-stimulated [14C]GABA release from cortical synaptosomes. These data suggest that ethanol selectively inhibits GABA release from neurons by a specific effect on potassium conductance, and inhibits ACh release by a selective effect on Na+ conductance.

Acetylcholine↗

PubMed1987

Chronic ethanol effect on the acidic phospholipids of synaptosomes isolated from cerebral cortex of C57BL/6NNIA mice--a comparison with age.

A total of six groups of C57BL/6NNIA male mice at 6, 18 and 28 months of age were administered a liquid diet containing either ethanol (8 g/kg body wt/day) or an isocaloric amount of glucose for three weeks. Sixteen hours after the last ethanol feeding, homogenates of cerebral cortices were prepared for isolation of the synaptosome-mitochondrial fraction. Phospholipids were separated by two-dimensional tlc and the level of individual phospholipids was determined by assaying the lipid phosphorus content. Based on protein content, there was a decrease (18%) in the level of phosphatidylserines between samples from 6 and 28 month-old mice; no age difference was observed in other phospholipids. Ethanol consumption resulted in a three-fold increase in poly-phosphoinositide level in the 6 month-old group, but the difference diminished considerably with age. The increase in poly-phosphoinositide level suggests a link between chronic ethanol administration and the receptor-mediated signal transduction mechanism involving phosphoinositide turnover. Results further indicate that animals in the younger age group are more readily influenced by the chronic effect of ethanol than those in the older age group.

Aging↗

PubMed1986

Dolichol alters dynamic and static properties of mouse synaptosomal plasma membranes.

Dolichols are isoprenologues that are found in almost all tissues and whose biochemical function, aside from dolichol phosphate precursors, is not known. In addition, an understanding of the organizational and dynamic properties of dolichols in biological membranes has not been forthcoming. The purpose of the experiments reported here were to examine the effects of dolichol on the physical properties of mouse synaptic plasma membranes (SPM). Differential polarized phase fluorometry indicated that dolichol both fluidized and rigidified SPM. Membrane areas detected by diphenylhexatriene and trans-parinaric acid were selectively fluidized and rigidified, respectively. It also was found that the spin label, 5-doxyl stearic acid indicated that dolichol reduced membrane fluidity. These results report for the first time a structural effect of dolichol on a biological membrane.

Animals↗

PubMed1986

Purification and properties of acyl-CoA:1-acyl-sn-glycero-3-phosphocholine-O-acyltransferase from bovine brain microsomes.

Acyl-CoA:1-acyl-sn-glycero-3-phosphocholine-O-acyltransferase has been purified approximately 3000-fold from bovine brain microsomes by detergent solubilization followed by ion-exchange and affinity chromatography. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed a single protein of molecular weight 43,000. The specificity of the purified enzyme was studied by measuring the catalytic activity with various lysophospholipids and acyl-CoA derivatives. Of the lysophospholipids tested, only lysophosphatidylcholine was a substrate. Less specificity was exhibited toward the acyl-CoA derivatives, although the enzyme showed a clear preference for arachidonoyl-CoA and little or no activity with palmitoyl-CoA or stearoyl-CoA. High concentrations of arachidonoyl-CoA inhibited the enzyme. The velocity was a sigmoidal function of the concentration of lysophosphatidylcholine (LPC) with little activity obtained below 20 microM LPC. The specificity and kinetic properties of the enzyme were altered, however, by incorporation of the enzyme into liposomes composed of a mixture of phospholipids. Decanoyl-CoA and myristoyl-CoA, which were effective substrates for the soluble enzyme, did not serve as acyl donors for the liposome-bound acyltransferase. Furthermore, the liposome-bound enzyme, in contrast to the soluble form of the enzyme, was active at concentrations of LPC below the critical micelle concentration. The liposome-bound enzyme was also substantially less susceptible to thermal denaturation and proteolytic digestion. This modulation of the acyltransferase activity by interaction with phospholipids may relate to the kinetic properties and the regulation of the enzyme in vivo.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1986

Changes in lipid composition of rat heart mitochondria after chronic ethanol administration.

Triacylglycerols and phospholipids of mitochondria from heart ventricular muscle were analyzed following chronic ethanol administration (2 and 10 g/kg of body weight/day) to adult rats for 21 days via intragastric intubation. Triacylglycerols were elevated 57% in the high ethanol group as compared to controls, but cholesterol level was not altered. Most of the phospholipids, including lysophospholipids, showed a small increase in level after ethanol administration. However the greatest increase (50%) occurred in ethanolamine plasmalogens. Although small changes in the acyl group composition of phosphatidylethanolamines and phosphatidylcholines were observed, the acyl group profile of cardiolipin remained unaltered. It is concluded that myocardial membranes respond to the disordering effects of ethanol by altering the synthesis of selected lipids more than through altering the phospholipid acyl group composition. Some of these changes may be responsible for altered mitochondrial functions in the myocardium.

Alcoholism↗

PubMed1986

Serum lipids and eggs.

This study shows the variability of response of serum cholesterol to whole food dietary cholesterol eaten by free-living people. Divided into two groups in a crossover design, normolipemic, healthy volunteers in Group A showed statistically significant increases in mean serum cholesterol after eating three eggs daily for 10 weeks (p less than or equal to .01) and a significant decrease within 2 weeks of crossover to eating no eggs (p less than or equal to .03). Group B exhibited a significant decrease in mean serum cholesterol after eating no eggs for 12 weeks (p less than or equal to .02) but, after crossing over to eating 3 eggs daily for 10 weeks, showed no longitudinally significant increases. Only Group A showed statistically significant changes in mean high-density-lipoprotein cholesterol, i.e., an increase at the end of 12 weeks of eating three eggs daily (p less than or equal to .001). Mean serum triglycerides showed no significant change.

Adult↗

PubMed1985

Metabolic relationship between arachidonate activation and its transfer to lysophospholipids by brain microsomes.

Evidence is presented to indicate a metabolic relationship between arachidonic acid activation and its transfer to lysophospholipids by brain microsomes. Thus, in the presence of 1-acylglycerophosphocholines or 1-acyl-glycerophosphoinositols, the activation of labeled arachidonate to its acyl-CoA was enhanced, and the acyl-CoA formed was, in turn, transferred to the lysophospholipids to form the respective diacyl-glycerophospholipids. The "coupling effect" seems to pertain mainly to the lysophospholipids which are good substrates of the acyltransferase. Other lyso-compounds were either not effective or inhibitory to the arachidonate activation process. The activation-transfer activity mediated by the fatty acid ligase and acyltransferase could be dissociated by Triton X-100, which apparently stimulated the acyl-CoA ligase activity but inhibited the acyltransferase. These results suggest that fatty acid ligase and acyltransferase are located in close proximity within the membrane domain. The existence of a close metabolic relationship between these two enzymic reactions is important for maintaining a dynamic equilibrium between the free fatty acids and the membrane phospholipids. The mechanism is also useful in regulating the cellular acyl-CoA and lysophospholipid metabolism, because both compounds have membrane perturbing properties when present in excessive quantity.

Acyl Coenzyme A↗

PubMed1985

Metabolism of lysophosphatidylcholine by swine platelets.

Incubation of intact platelets from Sinclair(S-1) miniature swine with 32P-labeled lysophosphatidylcholine (lyso PC) indicated the presence of an active lysophospholipase with a pH optimum of 8.0 for hydrolysis of the substrate. However, lyso PC was incorporated into the membrane phosphatidylcholines by the acyltransferase pathway upon addition of ATP, Mg++ and CoA to the platelet suspension. These results suggest that intact platelets are able to resist the cytotoxic effects of lyso PC in plasma, and the phospholipids in platelet membranes are not readily affected by the lipid environment of the plasma. The acyltransfer reaction apparently is saturated with endogenous free fatty acids since arachidonic acid added exogenously did not further enhance the incorporation activity. Neither the acyltransferase nor the lysophospholipase activity was affected by Ca++, but divalent metal ions such as Zn++ inhibited the lysophospholipase activity. Cholesterol but not cholesteryl esters elicited a biphasic effect on both enzymes, stimulating at low concentration but inhibiting at a cholesterol to lyso PC ratio greater than 1. Serum albumin inhibited the lysophospholipase but gave a small biphasic effect to the acyltransferase.

1-Acylglycerophosphocholine O-Acyltransferase↗

PubMed1984

Increased acidic phospholipids in rat brain membranes after chronic ethanol administration.

Two types of plasma membranes isolated from rat brain cortex were used to study the membrane-perturbing properties of ethanol. Rats administered ethanol in the form of a liquid diet showed an increase in levels of phosphatidylserines, phosphatidylinositols and phosphatidic acids as compared to controls. The results present evidence that chronic ethanol treatment results in an increase in the acidic phospholipids in brain membranes. This type of membrane modification may have important implications for the function of membrane transport enzymes such as (Na+, K+)-ATPase, which also increases in activity upon chronic ethanol administration.

Alcoholism↗

PubMed1984

Ethanol consumption and serum lipid profiles in Sinclair(S-1) miniature swine.

Ethanol consumption was correlated with changes in acyl group profiles of phosphatidylcholine and triacylglycerols in serum of Sinclair(S-1) miniature boars. Serum triacylglycerols in the control pigs were high in linoleate (18:2) (48%) and low in stearate (18:0 (3%). Upon feeding with 10% (w/v) ethanol ad lib for two weeks, the proportion of 18:2 in serum triacylglycerols decreased to 12-15% with a concomitant increase in 16:0, 18:0 and 18:1. Similar, but less extensive, acyl group changes were observed in the serum phosphatidylcholine. In addition, there was a decrease in the proportion of 20:3(n-6), but a biphasic change was shown in 20:4(n-6) with respect to ethanol consumption. In general, the high ethanol consumers (7.0 g/kg/day) indicated a more rapid rate of acyl group change than the low consumers (3.8 g/kg/day). Upon withdrawal of ethanol, acyl groups of triacylglycerols rapidly returned towards the control values, whereas only small changes were observed for the recovery in phospholipids. In this situation, the low-consumer group indicated a more rapid recovery than the high-consumer group. Results indicate that with the swine model, serum lipid changes can be a useful parameter for correlating biological changes upon ethanol consumption.

Alcohol Drinking↗