Biomedical subjects

N Ueta

Publications and source records attributed to N Ueta.

At least 19 recordsLinked to original sources

PubMed2004

A novel antioxidant action of ethanolamine plasmalogens in lowering the oxidizability of membranes.

We have demonstrated a novel antioxidant action of ethanolamine plasmalogens both in protecting cholesterol from oxidation by free radicals and in lowering the oxidizability of membranes, along with the action of scavenging radicals, by the oxygen-uptake method using large unilamellar vesicles and the water-soluble azo-radical initiator, AAPH [2,2'-azobis-(2-amidino-propane) dihydrochloride].

Antioxidants↗

PubMed2001

Rewarming eliminates the protective effect of cooling against delayed neuronal death.

Mild intra-ischemic hypothermia provides neuroprotection against delayed neuronal death in the hippocampal CA1. It has recently been reported that reduction in the metabolic rate of arachidonic acid (AA) liberated during ischemia might contribute to this neuroprotection. To examine whether rewarming during the early period of recirculation accelerates AA consumption and eliminates the neuroprotection, we measured the levels of AA in the hippocampus after various recirculation times under normothermia and hypothermia with or without rewarming. The tendency for AA to disappear was significantly different between each pair of groups. Histological examination 7 days after ischemia revealed no protection in the rewarmed group. These results suggest that neuronal injury during rewarming after hypothermia may be attributed to the rate of AA metabolism.

Animals↗

PubMed2001

Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil.

Although ethanolamine plasmalogens (EtnPm) are the predominant phospholipids in neural tissue, their physiological role has not been clarified. The biophysical conformation of EtnPm in the proteoliposome enhances the activity of the sodium-calcium exchanger, which has been proposed to induce intracellular calcium ion accumulation during ischemia and early reperfusion. The levels of EtnPm in the areas of the gerbil brain selectively vulnerable to ischemia, namely the hippocampal CA1 and CA3 regions and the cerebral cortex, were measured by high-performance thin-layer chromatography and gas-liquid chromatography. The concentration of EtnPm in the CA1 region, which is the most vulnerable to ischemic and anoxic stress, was 2.6- and 2.7-fold higher than that in the CA3 region and cerebral cortex, respectively. The significantly higher concentration of EtnPm in the hippocampal CA1 region may enhance sodium-calcium exchanger activity and play an important role in the vulnerability of this region to ischemia.

Animals↗

PubMed2001

Antioxidative activity of 3,4-dihydroxyphenylacetic acid and caffeic acid in rat plasma.

The purpose of the present paper is to study and compare in vitro the inhibitory effect of 3,4-dihydroxyphenylacetic acid (DOPAC) and caffeic acid (CA) on lipid peroxidation in rat plasma. Rat plasma was oxidized at 37 degrees C by the radical initiators 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) or 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). The consumption of endogenous alpha-tocopherol (alpha-TOH) and the accumulation of conjugated diene hydroperoxides were measured by high-performance liquid chromatography and by ultraviolet spectroscopy, respectively. Alpha-TOH was consumed at the same rate in the presence of 20 mM AAPH or 2 mM MeO-AMVN. DOPAC and CA suppressed the alpha-TOH consumption in a dose-dependent manner. A concentration of 50 microM of both phenolic acids was sufficient to induce a lag phase and to delay the rate of alpha-TOH consumption. The effect was more pronounced in rat plasma oxidation by AAPH than by MeO-AMVN. CA spared vitamin E more effectively than DOPAC in both oxidations. DOPAC and CA suppressed the formation of conjugated diene hydroperoxides. DOPAC and CA at concentration 50 microM suppressed alpha-TOH consumption during oxidation of soybean phosphatidylcholine (2.8 mM) multilamellar vesicles containing 15 microM alpha-TOH, in which the lipophilic initiator 2,2'-azobis (2,4-dimethylvaleronitrile) (6 mM) was incorporated. In conclusion, we demonstrated that DOPAC and CA in micromolar concentrations have antioxidant activity in rat plasma, a medium very close to the conditions in vivo, suggesting that supplementation with the phenolic acids will provide significant antioxidant protection.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus.

Ceramide, a hydrolyzed product of sphingomyelin, is reported to play an important role in apoptosis. In this study, we measured the sphingomyelin and ceramide levels in the hippocampus of the gerbil after transient forebrain ischemia for 5 min (lethal) or 2 min (sublethal). The aim was to examine alterations in the sphingomyelin cycle during delayed neuronal death, which we considered could be due to apoptosis. Sphingolipids were separated on high-performance thin-layer chromatography plates and analyzed by gas-liquid chromatography. At 30 min and 24 h after lethal ischemia, sphingomyelin levels were decreased and ceramide levels were increased compared with control levels. No significant changes were observed after sublethal ischemia. These results suggest that the sphingomyelin cycle may have a role in neuronal death.

Animals↗

PubMed2000

Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion.

L-PDMP (L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

Animals↗

PubMed2000

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids.

To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.

Animals↗

PubMed1998

Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion.

Free fatty acid (FFA) accumulation during cerebral ischemia has been described as an indicator of ischemic damage. Furthermore arachidonic acid (AA) metabolites, liberated from glycerophospholipids, have been confirmed to induce disturbances of membrane functions. Are there differences in AA levels in the hippocampus of normo- and hypothermic gerbils following ischemia-reperfusion? In an attempt to answer this question, we first studied the time course of changes in the amount of AA liberated from glycerophospholipids using gerbils subjected to 5 min of ischemia-reperfusion under normo- and mild hypothermia. FFAs (including AA) were separated from total lipids by Bond Elut (NH2) column chromatography and analyzed by gas-liquid chromatography. Mild intra-ischemic hypothermia (MIH) did not affect the ischemia-induced AA accumulation following of 5 min of forebrain ischemia. The accumulated AA amounts under MIH tend to decrease more slowly to baseline levels from 15 to 30 min of reperfusion than do the levels under normothermia. These results suggested that MIH reduced the rate of metabolism of AA after reperfusion and might suppress the generation of free radical, eicosanoids and other bioactive metabolites.

Animals↗

PubMed1996

Sphingomyelin changes in rat cerebral cortex during focal ischemia.

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia.

Animals↗

PubMed1995

Oxidized low-density lipoprotein induces the production of superoxide by neutrophils.

Exposure of guinea pig peritoneal neutrophils to ox-LDL led to the production of superoxide, which was measured by the formation of superoxide-dependent chemiluminescence. The cells exposed to unoxidized LDL, e.g. native LDL, acetyl-LDL, and self-aggregates of LDL showed no production of superoxide. The superoxide production was correlated with the levels of oxidative modification of LDL and reached a maximum between 10 and 30 min during incubation, but preincubating the cells with cytochalasin B decreased the superoxide production. These findings indicate that neutrophils rapidly take up ox-LDL by phagocytosis and generate superoxide which may cause superoxide-mediated lipid peroxidation in vivo.

Animals↗

PubMed1995

Lipid peroxidation and ceroid accumulation in macrophages cultured with oxidized low density lipoprotein.

When mouse peritoneal macrophages were cultured with oxidized human low density lipoprotein (ox-LDL), storage of ceroid-like pigments was observed within the cells by light and fluorescent microscopy, and fluorescence spectrophotometry. The fluorescent products exhibit the characteristics of Schiff base structures, having a fluorescence maximum of 430 nm and an excitation maximum of 355 nm, which has been generally accepted with fluorescent lipid peroxidation products. Similar fluorescent products were isolated from the atherosclerotic lesions of the aged human artery. Ox-LDL was also intraperitoneally injected into guinea pigs to study an early stage of ceroid accumulation in macrophages. An early event in guinea pigs was the appearance of neutrophils. The findings from the model systems suggest that the ox-LDL in the artery wall is probable chemotactic for neutrophils as well as monocytes. We propose the hypothesis that the production of superoxide by neutrophils causes further lipid peroxidation of native LDL and then produces large amounts of oxidatively modified LDL which is the souse of ceroid pigment accumulated within the foam cells in human atherosclerotic lesions.

Aged↗

PubMed1995

[Sphingolipid changes in rat cerebral cortex during focal ischemia--how does ceramide accumulate in an ischemic condition?].

Levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by middle cerebral artery occlusion. Ceramide began to increase at 6 hours of ischemia and increased to 4.5 folds at 96 hours. Amino-linked fatty acids in increased ceramide were composed solely of non-hydroxy fatty acids, and stearic acid was the most prominent. Sphingomyelin, whose amino-linked fatty acids were mostly stearic acid, decreased in a time-dependent manner and became about a half of controls at 96 hours. Hydroxy fatty acid linked cerebroside decreased at and after 6 hours of ischemia, whereas significant decrease of non-hydroxy fatty acid linked cerebroside occurred only at 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. The results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during ischemia.

Animals↗

PubMed1994

Conformational changes in oxidized LDL recognized by mouse peritoneal macrophages.

Mouse peritoneal macrophages have been considered to recognize and take up oxidized LDL by a scavenger receptor. However, it is still unknown what conformational changes in oxidized LDL contribute to recognition by the macrophage scavenger receptor. In the present study, it was shown that the amount of oxidized LDL taken up by macrophages correlated well with the fluorescence intensity formed in oxidized LDL. The autofluorescent products generated in oxidized LDL were characterized by Ex:365 nm Em:430 nm, and the intensity of the fluorescence was reduced at base pH, and restored by adjusting the pH to neutral. The characteristics of the fluorescent products indicate that a Schiff base structure was formed in oxidized LDL. Oxidized LDLs were fractionated into native size and aggregated large particles with HPLC by monitoring fluorescence. It was demonstrated that macrophages ingest selectively or preferentially aggregated oxidized LDL, but not native size oxidized LDL. The incorporation of aggregated oxidized LDL was remarkably suppressed by heparin and cytochalasin B. These results suggest that mouse peritoneal macrophages recognize the conformational changes in oxidized LDL related to the formation of a Schiff base structure with increasing autofluorescence, and ingest selectively aggregated large particles in oxidized LDL in a phagocytic process.

Animals↗

PubMed1992

Fatty chains of alkenylacyl, alkylacyl and diacyl phospholipids in sea urchin spermatozoa.

1. Alkenylacyl, alkylacyl and diacyl phospholipids were analyzed in the spermatozoa of the sea urchin, Hemicentrotus pulcherrimus. 2. Choline phosphoglycerides (CPG) contained alkylacyl component (19%) in addition to the diacyl component (81%), and alkenylacyl analog was present in a trace amount. The ethanolamine phosphoglycerides (EPG) contained alkenylacyl (51%), alkylacyl (2%) and diacyl (47%) components and the serine phosphoglycerides (SPG), alkylacyl (9%) and diacyl (91%) derivatives. 3. Analysis by gas-liquid chromatography indicated that the fatty chain at the 1-position in alkenylacyl, alkylacyl and diacyl compounds of CPG, EPG and SPG was mainly composed of saturated and monoenoic types (16:0, 18:0, 18:1 and 20:1). In contrast, considerable amounts of polyunsaturated types (20:4 and 20:5) were noted at the 2-position.

Animals↗

PubMed1991

Purine and pyrimidine compounds in murine peritoneal macrophages cultured in vitro.

Extracts of murine peritoneal macrophages were analysed by ion-pair reversed-phase high-performance liquid chromatography during incubation at 37 degrees C in vitro. Four-step gradient elution was applied to an ODS column (250 x 4.6 mm I.D.) at a flow-rate of 1.3 ml/min, allowing the separation of hypoxanthine, inosine, guanosine, adenosine, IMP, CDP, AMP, GDP, UDP, ADP, CTP, GTP, UTP and ATP within 50 min. Samples of 0.4 . 10(6)-0.5 . 10(6) cells were washed twice with RPMI 1640 medium and extracted with perchloric acid. Nucleotide concentrations of murine peritoneal macrophages did not change during incubation for 4 days in vitro.

Animals↗

PubMed1991

Free radical-induced liver injury. II. Effects of intraperitoneally administered 2,2'-azobis(2-amidinopropane) dihydrochloride on the fatty acid profiles of hepatic triacylglycerol and phospholipids.

Liver injury induced by the radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and carbon tetrachloride (CCI4) was examined by the analysis of lipids in the liver of rats. Increased triacylglycerol (TAG) was found in the liver within 24 hr following injection of these drugs. In AAPH-treated and CCI4-treated rats, it was 2.1 and 1.8 times that in the controls, respectively. TAG-palmitate and -oleate were found at particularly increased levels, while polyunsaturated fatty acid profiles of hepatic phospholipids were essentially the same for the treated and untreated rats. It is evident from these findings that radical initiators cause no decrease in polyunsaturated fatty acids in hepatic lipids, but accumulate TAG in the liver. Such a condition is the equivalent of liver injury in the rats in whose diets vitamin E has long been deficient.

Amidines↗

PubMed1991

Free radical-induced liver injury. I. Effects of dietary vitamin E deficiency on triacylglycerol level and its fatty acid profile in rat liver.

Effects of dietary vitamin E deficiency on the fatty acid compositions of total lipids and phospholipids were studied in several tissues of rats fed a vitamin E-deficient diet for 4, 6, and 9 months. No significant differences were observed between the vitamin E deficiency and controls except in the fatty acid profiles of liver total lipids. Triacylglycerol (TAG) accumulation was found in the liver of rats fed a vitamin E-deficient diet. The levels of TAG-palmitate and -oleate increased particularly in the liver from such animals. The fatty acid compositions of hepatic phospholipids were not affected by the diet. Increased TAG observed in the liver of rats fed a vitamin E-deficient diet was restored to normal when the diet was supplemented with 20 mg alpha-tocopheryl acetate/kg diet. These findings indicate that dietary vitamin E deficiency causes TAG accumulation in the liver and that the antioxidant, vitamin E, is capable of preventing free radical-induced liver injury.

Animals↗

PubMed1991

Localization and characterization of phosphatidylcholine in sea urchin spermatozoa.

Sea urchin spermatozoa obtain energy for movement through oxidation of endogenous phospholipids, particularly phosphatidylcholine (PC). This study was undertaken to determine the localization of PC available for utilization in energy metabolism in spermatozoa of the sea urchin, Hemicentrotus pulcherrimus. Following incubation with sea water, the PC content in sperm heads decreased significantly, while that in sperm tails did not change. PC was abundant in sperm heads, particularly the midpieces. PC composed of unsaturated fatty acids was consumed to a greater extent during incubation than that consisting of saturated fatty acids. Analysis by gas-liquid chromatography indicated most of fatty acid moieties in the midpieces PC to be unsaturated. Phospholipase A2 activity was also distributed in sperm heads, particularly the midpieces. It thus appears that PC as a substrate for energy metabolism is located in the midpieces of sea urchin spermatozoa.

Animals↗