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Biomedical subjects

K Waku

Publications and source records attributed to K Waku.

At least 19 recordsLinked to original sources
PubMed1992

Distribution of alkyl and alkenyl ether-linked phospholipids and platelet-activating factor-like lipid in various species of invertebrates.

The levels of alkenylacyl, alkylacyl and diacyl subclasses of choline glycerophospholipid (CGP) and ethanolamine glycerophospholipid (EGP) fractions in 28 species of various invertebrates were studied. We found that only small amounts of either 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) or 1-alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkenylacyl-GPE) are present in most species of insects. On the other hand, almost all species examined in various phyla other than Arthropoda were shown to contain large amounts of both alkylacyl-GPC and alkenylacyl-GPE. The highest proportion of alkylacyl subclass in CGP was noted in sponge, Halichondria japonica (81.8% of CGP) and the highest proportion of alkenylacyl subclass in EGP was found in clam worm, Marphysa sanguinea (88.7% of EGP). We next surveyed the presence of platelet-activating factor (PAF)-like lipid in 45 species of invertebrates. PAF-like lipid was widely distributed among various lower animals. The highest value was obtained for sea cucumber, Stichopus japonicus, in which PAF-like lipid was present throughout the body. We also confirmed the presence of acetyltransferase activity in several lower animals. These results suggest that alkyl and alkenyl ether-linked phospholipids including PAF are physiologically important molecules particularly for invertebrates belonging to lower phyla.

Animals↗
PubMed1992

Inhibition of the liberation of arachidonic acid by cadmium ions in rabbit alveolar macrophages.

The effects of CdCl2 on the liberation of arachidonic acid (20:4) from membrane phospholipids of A23187-stimulated rabbit alveolar macrophages and on the activity of phospholipase A2 (PLA2) in a cytosolic fraction were studied. Alveolar macrophages were prelabeled with [3H]arachidonic acid (20:4) and then treated with A23187. This treatment resulted in a remarkable increase in the liberation of [3H]20:4 from their phospholipids. Exposure of cells to Cd2+ inhibited the liberation of [3H]20:4 in a dose-dependent manner. Liberation of [3H]20:4 from cell lipids was calcium dependent and the inhibitory effect of Cd2+ competed with the stimulatory effect of Ca2+. When Ca2+ was removed from the incubation medium, Cd2+ did not influence the liberation of [3H]20:4. Entry of 45Ca2+ into cells was enhanced by treatment of A23187. However, Cd2+ did not influence the cellular uptake of 45Ca2+. Treatment with A23187 markedly enhanced entry of 109Cd2+ into cells. The effect of Cd2+ on the activity of phospholipase A2 was determined with 1-palmitoyl-2-[14C]arachidonoyl-sn-glycero-3-phosphocholine as substrate. Calcium-dependent activation of PLA2 was observed and Cd2+ inhibited activation in a dose-dependent manner. These results suggest that exposure of alveolar macrophages to Cd2+ causes a reduction in the rate of liberation of 20:4 from cell lipids, as a possible result of the inhibition of PLA2 activity by Cd2+.

Animals↗
PubMed1992

[The composition of phospholipid and biosynthesis of platelet-activating factor in earthworm (Eisenia foetida)].

Platelet-activating factor (PAF) was for the first time confirmed to exist in a lower animal, earthworm (Eisenia foetida). It amounts to 10.7 +/- 6.1 pmol/g wet body weight, and varied seasonally. Phospholipid analysis revealed that 1-O-alkyl-2-acyl-sn-glycerophosphocholine, a stored form of PAF precursor, accounted for 61.4% of the choline glycerophospholipids. Two kinds of enzyme activities operating in PAF generation in mammalian cells were also detected from this species. The PAF level increased markedly under some injurious stimuli such as cutting and pricking. The results suggest that PAF may be a primary mediator involved in pathological and physiological reactions even in lower animal like earthworm. The findings also cast a new light on the mechanisms underlying the antihypertensive and other effects of the Chinese medicinal earthworm, pheretima.

Animals↗
PubMed1992

Differential effects of platelet-activating factor on superoxide anion production in human eosinophils and neutrophils.

The effect of platelet-activating factor (PAF) on the generation of superoxide anion (O2-) in human eosinophils and neutrophils was examined. The presence of PAF potentiated O2- production in either opsonized zymosan- or formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated cells. The effect of PAF was prominent in opsonized zymosan-stimulated eosinophils and in FMLP-stimulated neutrophils. We also found that eosinophils generate substantial amounts of O2- when treated with PAF alone. The high responsiveness of unstimulated or opsonized zymosan-stimulated eosinophils to PAF to generate O2- may be relevant to the pathological changes at the loci of allergic reactions where eosinophils and PAF are crucially involved.

Eosinophils↗
PubMed1991

Transient activation of 1-O-alkyl-sn-glycero-3-phosphocholine: acetyl-CoA acetyltransferase during the incubation of macrophages.

The activity of the platelet-activating factor (PAF)-synthesizing enzyme, 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF):acetyl-CoA acetyltransferase (EC 2.3.1.67) in alveolar macrophage lysate was found to be elevated after warming the cells to 37 degrees C. Such an increase in enzyme activity was detectable only when intact cells were warmed. The stimulation was transient, reaching a peak at 2 min, and then gradually decreased to the control level. We could not find increased PAF formation in warmed cells which had increased acetyltransferase activity, even though substantial amounts of lysoPAF were shown to be present within cells. In contrast, considerable amounts of PAF were formed after treatment of the cells with exogenous lysoPAF. These results suggest that the activation of acetyltransferase is not sufficient to induce PAF formation and that the increased availability of substrates, especially lysoPAF, in the cells is indispensable for triggering PAF biosynthesis in this type of cells.

Acetyl Coenzyme A↗
PubMed1991

Regulation of the biosynthesis of platelet-activating factor in alveolar macrophages.

Activities of enzymes which metabolize lysoplatelet-activating factor (lysoPAF) and platelet-activating factor (PAF) were studied in rabbit alveolar macrophage lysates. Substantial acetyltransferase activity was noted in the presence of 100 microM acetyl-coenzyme A (CoA), and this activity was increased in A23187-stimulated cell lysate. On the other hand, in the absence of exogenous acetyl-CoA, lysoPAF was mainly acylated through a transacylation pathway rather than by acetyltransferase in both control and A23187-stimulated cell lysates. We confirmed that the intracellular concentration of acetyl-CoA is relatively low. The observations suggest that the transacylation system may play an equally important role in the regulation of the availability of lysoPAF in intact cells. Intracellular lysoPAF was also maintained at relatively low levels. Interestingly, large amounts of PAF were produced even in unstimulated cells upon addition of an excess of exogenous lysoPAF, suggesting that generation of an adequate amount of lysoPAF within cells may be sufficient to trigger PAF synthesis in this type of cells.

Acetyl Coenzyme A↗
PubMed1991

Production of platelet-activating factor by human normodense and hypodense eosinophils.

Normodense eosinophils and neutrophils from normal donors produced considerable amounts of platelet-activating factor (PAF) when stimulated with ionophore A23187. PAF produced by eosinophils appeared to be degraded more rapidly than PAF formed by neutrophils, suggesting a higher activity of PAF-degrading enzyme in eosinophils. Substantial proportions of PAF newly formed by both eosinophils and neutrophils were shown to be cell-associated. By comparison, hypodense eosinophils obtained from a patient with idiopathic hypereosinophilic syndrome produced an extremely large amount of PAF and released much of it into the incubation medium. The accelerated formation of PAF in hypodense eosinophils may be related to various cardiovascular complications associated with hypereosinophilic syndrome.

Eosinophilia↗
PubMed1991

Prevention by zinc of cadmium inhibition of stearoyl-CoA desaturase in rat liver.

Rats were fed a fat-free diet that contained zinc (50 ppm; ZA rats) or a fat-free diet without zinc (less than 2 ppm; ZD rats) for 16 days. Some rats in these two groups were injected subcutaneously with cadmium (Cd) at a dose of 0.01 mmol/kg body weight 48 h before they were killed. The treatment of ZD rats with Cd reduced the activity of liver microsomal stearoyl-CoA desaturase by 90% without any changes in the activity of NADH-cytochrome b5 reductase or in the microsomal level of cytochrome b5 whereas the activity of stearoyl-CoA desaturase was reduced by only 35% by the treatment of ZA rats with Cd. Exposure of ZD rats to Cd decreased the proportions of 18:1 (n-9) and 20:3 (n-9) in the major phospholipids of the liver, whereas the ZA rats showed few changes in fatty acid composition when they were treated with Cd. Although the changes in fatty acid composition were most marked in phosphatidylcholine among the various phospholipids, the activity of microsomal l-acylglycerophosphocholine (1-acyl GPC) acyltransferase was not affected by treatment with Cd. These results suggest that zinc is essential for the protection of hepatic stearoyl-CoA desaturase from challenges by Cd and that delta 9 desaturase plays a crucial role in the control of the acyl composition of hepatic phospholipids.

Animals↗
PubMed1991

Suppression of ethanolamine-containing glycerophospholipid synthesis in HL-60 cells during retinoic acid-induced differentiation.

Synthesis and degradation of glycerophospholipids in HL-60 cells and retinoic acid (RA)-treated HL-60 cells were examined. The synthesis of each subclass of ethanolamine-containing glycerophospholipids was extremely suppressed in RA-treated HL-60 cells, while that of other glycerophospholipids was not seriously affected. A pulse-chase experiment revealed that about 88% of 1,2-diacyl and 28% of 1-alkenyl-2-acyl glycerophosphoethanolamine were degraded during 4 days in RA-treated HL-60 cells. These characteristics of metabolism observed in RA-treated HL-60 cells might be responsible for the change of subclass composition of ethanolamine-containing glycerophospholipids in HL-60 cells during differentiation to granulocytes.

Cell Differentiation↗
PubMed1991

Production of platelet-activating factor in slugs.

The land slug, Incilaria bilineata, was shown to contain a large amount of 1-O-alkyl-2-acyl (long chain)-sn-glycero-3-phosphocholine, which accounts for as much as 47% of the choline glycerophospholipid fraction. Since this unique either phospholipid has been regarded as a stored precursor form of platelet-activating factor (PAF) in mammalian inflammatory cells, we examined the possibility of the presence of PAF in this animal. We obtained the evidence for the occurrence of significant amounts of PAF in two species of slugs, Incilaria bilineta and Incilaria fruhstorferi. Gas chromatography-mass spectrometry analysis revealed that the alkyl fatty chain of PAF principally consists of 16:0. We confirmed the presence of both enzyme activities catalyzing the formation of PAF, one for the remodeling pathway and the other for the de novo pathway. We also found the occurrence of other enzyme activities involved in PAF metabolism: acetylhydrolase activity which inactivates PAF and phospholipase A2 activity toward alkylacylglycerophosphocholine. However, we failed to detect cofactor-independent transacylation activity in this animal. The amounts of PAF in slugs were markedly increased when slugs were administered several treatments which are considered to induce shock, such as the injection of dimethyl sulfoxide or injuries. These results suggest that PAF is produced and may have certain physiological and pathological roles in the land slug, as in the case of mammals.

Acetyltransferases↗
PubMed1990

Ether lysophospholipid-induced production of platelet-activating factor in human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMN) produced considerable amounts of platelet-activating factor (PAF) when exposed to various concentrations of lyso-PAF, especially in the absence of albumin. The amount of produced PAF in the presence of 5 microM lyso-PAF (without albumin) was 1.1 pmol/10 min per 2.5 X 10(6) cells, which was close to the level in the case of opsonized zymosan stimulation. We found that the activity of neither acetyltransferase nor acetylhydrolase was affected markedly by the treatment of cells with lyso-PAF, suggesting that the increased availability of lyso-PAF could be responsible for the induction of PAF synthesis. We also found that PAF synthesis was induced not only by lyso-PAF but also by ether-containing ethanolamine lysophospholipids, 1-alkenyl(alkyl)-sn-glycero-3-phosphoethanolamine (GPE). The addition of 1-alkenyl(alkyl)-GPE caused the degradation of pre-existing 1-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine (GPC) and an increased level of lyso-PAF, followed by the formation of PAF. By contrast, 1-acyl-GPC and 1-acyl-GPE failed to induce PAF production. These results suggest a possible key role of the availability of lyso-PAF in triggering the biosynthesis of PAF in human PMN.

Acetates↗
PubMed1990

Effects of zinc deficiency on the fatty acid composition and metabolism in rats fed a fat-free diet.

The effects of dietary zinc deficiency (ZD) on the composition and metabolism of the fatty acyl chains of phospholipids in rat liver were investigated with a fat-free diet. The levels of (n - 9) fatty acids such as 18:1 and 20: 3(n - 9) in liver phospholipids (PL) were significantly lower in ZD-rats (19.4% and 5.4%, respectively) than in PF-rats (25.2 and 8.3%). On the other hand, the levels of (n - 6) acids such as 18:2 and 20:4 were higher in ZD-rats (3.3 and 19.1%, respectively) than in PF-rats (2.1 and 14.9%). In order to study the metabolism of fatty acids in vivo, 14C-18:0 or 14C-18:2 was intravenously injected, and then the conversion to the respective metabolite was examined. After the injection of 14C-18:0, the radioactivity was found in 18:0 (49.3% of the total), 18:1 (33.2%), and 20:3 (n - 9) (9.1%) in liver PL in PF-rats at 24 h. In ZD-rats, the radioactivity was dramatically lower in 18:1 (23.5%) and 20:3 (n - 9) (3.6%), suggesting that the conversion of 18:0 to 18:1 and 20:3 (n - 9) was strongly inhibited in ZD-rats. When 14C-18:2 was injected, the radioactivity was mainly found in 18:2, 20:3 (n - 6), and 20:4. The radioactivity in 20:4 in ZD-rats was slightly higher than that in control rats. These results indicate that zinc deficiency affects the fatty acid metabolism in liver, in particular, it causes a reduction in delta 9 desaturase activity, when rats are fed a fat-free diet.

Animals↗
PubMed1990

The effect of cadmium on the composition and metabolism of hepatic fatty acids in zinc-adequate and zinc-deficient rats.

Exposure to cadmium (Cd) caused changes in the fatty acid composition of phospholipids, such as increases in levels of saturated and (n-6) fatty acids and decreases in levels of (n-9) fatty acids, in the liver phospholipids of rats fed a fat-free diet. These changes were similar to those caused by dietary zinc deficiency. The changes in fatty acid composition after administration of Cd were greater in zinc-deficient (ZD) rats than zinc-adequate (ZA) rats. When [14C]18:0 was injected intravenously in order to examine the metabolism of (n-9) fatty acids, a decrease in the rate of conversion of [14C]18:0 to [14C]18:1 was observed in liver phospholipids after treatment of ZD rats with Cd. These results suggested that Cd can affect the metabolism of fatty acids in relation to zinc status and, in particular, causes a reduction in the activity of delta 9-desaturase which converts 18:0 to 18:1.

Animals↗
PubMed1989

Augmented production of platelet-activating factor in human polymorphonuclear leukocytes by ketone bodies.

The production of platelet-activating factor (PAF) in A23187-stimulated human polymorphonuclear leukocytes was markedly increased in the presence of 5 mM acetoacetate and beta-hydroxybutyrate. Such an augmentation was observed even at 500 microM but not at 50 microM. The augmented production of PAF by acetoacetate was also observed in the presence of autologous serum and was most prominent in the case of opsonized zymosan-stimulation rather than A23187-stimulation. These observations suggest that increased levels of acetoacetate and beta-hydroxybutyrate in blood may lead to the augmented production of PAF, which would amplify the various PAF-mediated biological reactions.

3-Hydroxybutyric Acid↗
PubMed1989

Selective acyl transfer in the reacylation of brain glycerophospholipids. Comparison of three acylation systems for 1-alk-1'-enylglycero-3-phosphoethanolamine, 1-acylglycero-3-phosphoethanolamine and 1-acylglycero-3-phosphocholine in rat brain microsomes.

The activities of three acylation systems for 1-alkenylglycerophosphoethanolamine (1-alkenyl-GPE), 1-acyl-GPE and 1-acylglycerophosphocholine (1-acyl-GPC) were compared in rat brain microsomes and the acyl selectivity of each system was clarified. The rate of CoA-independent transacylation of 1-[3H]alkenyl-GPE (approx. 4.5 nmol/10 min per mg protein) was about twice as high as in the case of 1-[3H]acyl-GPE and 1-[14C]acyl-GPC. On the other hand, the rates of CoA-dependent transacylation and CoA + ATP-dependent acylation (acylation of free fatty acids by acyl-CoA synthetase and acyl-CoA acyltransferase) of lysophospholipids were in the order 1-acyl-GPC greater than 1-acyl-GPE much greater than 1-alkenyl-GPE. HPLC analysis of newly synthesized molecular species revealed that the CoA-independent transacylation system exclusively esterified docosahexaenoate and arachidonate, regardless of the lysophospholipid class. The CoA-dependent transacylation and CoA + ATP-dependent acylation systems were almost the same with respect to the selectivities for unsaturated fatty acids when the same acceptor lysophospholipid was used, but some distinctive acyl selectivities were observed with different acceptor lysophospholipids. 1-Alkenyl-GPE selectively acquired only oleate in these two systems. 1-Acyl-GPE and 1-acyl-GPC showed selectivities for both arachidonate and oleate. In addition, an appreciable amount of palmitate was transferred to 1-acyl-GPC, not to 1-acyl-GPE, in CoA- or CoA + ATP-dependent manner. The acylation of exogenously added acyl-CoA revealed that the acyl selectivities of the CoA-dependent transacylation and CoA + ATP-dependent acylation systems may be mainly governed through the selective action of acyl-CoA acyltransferase. The preferential utilization of oleoyl-CoA by all acceptors and the different utilization of arachidonoyl-CoA between alkenyl and acyllysophospholipids indicated that there might be two distinct acyl-CoA:lysophospholipid acyltransferases that discriminate between oleoyl-CoA and arachidonoyl-CoA, respectively. Our present results clearly show that all three microsomal acylation systems can be active in the reacylation of three major brain glycerophospholipids and that the higher contribution of the CoA-independent system in the reacylation of ethanolamine glycerophospholipids, especially alkenylacyl-GPE, may tend to enrich docosahexaenoate in these phospholipids, as compared with in the case of diacyl-GPC.

Acyltransferases↗