Search PubMed⌕ Search

Biomedical subjects

S Murota

Publications and source records attributed to S Murota.

At least 163 records · Page 9Linked to original sources
PubMed1986

Appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells during monocytic differentiation: enhancement of thromboxane synthesis by 1 alpha,25-dihydroxyvitamin D-3.

The appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells was investigated during 1 alpha,25-dihydroxyvitamin D-3-induced monocytic differentiation. 1 alpha,25-Dihydroxyvitamin D-3-treated HL-60 cells acquired the ability to convert [1-14C]arachidonic acid to thromboxane B2 and prostaglandin E2 during monocytic differentiation. The major cyclooxygenase product synthesized by the HL-60 cells after 3-4 days exposure to 1 alpha,25- dihydroxyvitamin D-3 (48 nM) was thromboxane B2 and its production was about 19-25-times higher than that of untreated HL-60 cells. The percent conversion of thromboxane B2 from [1-14C]arachidonic acid in the 1 alpha,25-dihydroxyvitamin D-3 (48 nM, 3 day exposure)-treated HL-60 cells was about 4.4% as compared to that (about 0.3%) of the untreated cells, whereas the percent conversion of thromboxane B2 from [1-14C]prostaglandin H2 in the 1 alpha,25-dihydroxyvitamin D-3-treated cell homogenate was about 22.4% as compared to that (about 13.6%) of the untreated cell homogenate. The stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on thromboxane B2 production from [1-14C]arachidonic acid and from [1-14C]prostaglandin H2 in HL-60 cells was inhibited by the addition of cycloheximide (1 microgram/ml). However, 1 alpha,25-dihydroxyvitamin D-3 (48 nM) did not significantly stimulate the arachidonic acid release either in HL-60 cells or in 1 alpha,25-dihydroxyvitamin D-3-induced cells. These results suggest that the stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on the thromboxane production in HL-60 cells was not due to the activation of phospholipase A2 but due to the induction of fatty acid cyclooxygenase and thromboxane synthetase activities. Thromboxane A2 actively produced during the monocytic differentiation of HL-60 cells could influence the cell adhesiveness of the monocyte-macrophage-differentiated cells.

Arachidonic Acid↗
PubMed1986

Regulation of platelet aggregation and arachidonate metabolism in streptozotocin-diabetic rats.

Thromboxane A2 generation during collagen-induced platelet aggregation was increased in platelets from streptozotocin-induced diabetic rats when washed platelets were resuspended in pooled-control rat plasma. 14C-Arachidonate incorporation into platelets and oxygenation into thromboxane B2 in these rats were significantly higher than in the control rats, whereas fatty acid analysis revealed markedly decreased arachidonate composition in platelet phospholipids. Meanwhile plasma isolated from diabetic rats inhibited collagen-induced platelet aggregation in a volume-dependent fashion. These results suggest that enhanced platelet thromboxane synthesis in streptozotocin-diabetic rats is accompanied by increased arachidonate metabolism in platelets, which may serve to aid efficient utilization of a decreased thromboxane A2 precursor pool. Plasma factor(s) in these rats may modify the platelet reactivity in vivo.

Animals↗
PubMed1986

Contribution of lipoxygenase metabolites to IL-2 production in the early phase of lymphocyte activation.

Lipoxygenase inhibitors; eicosatetraynoic acid (ETYA), esculetin and caffeic acid, inhibited interleukin-2 (IL-2) production by Con A (concanavalin A)-stimulated murine spleen lymphocytes. They effectively inhibited IL-2 production without affecting cell viability when they were added to the cultures within around 6 hr after Con A stimulation. IL-1 production was also inhibited effectively when the inhibitors were added within 4 hr after stimulation. Therefore, immunosuppressive characteristics of these inhibitors can in part be explained by their inhibitory effects on production of lymphokines involved in the early phase of lymphocyte activation.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1986

Ultrastructural appearances of subcultured aortic smooth muscle cells migrating into Millipore filters.

The ultrastructures of vascular smooth muscle cells migrating in Millipore filters were examined using a modified Boyden chamber. The cells (seventh and eighth subculture) were obtained from explants of rat aorta. Very small numbers of bipolar-shaped cells migrated deeply into the filter toward a platelet suspension added to the lower compartment. The migrating cells were richer in intermediate filaments and microtubules than the cells on the filter. The cytoskeleton was oriented along the elongated cell body, and the cortical microfilamentous mat was disorganized along the entire cell periphery. These data are discussed.

Animals↗
PubMed1986

[Prostaglandins].

Explore the source record for details and available documents.

Chemical Phenomena↗
PubMed1985

Enhancement of endogenous production of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) has a chemotactic effect on smooth muscle cells, which is inhibited by lipoxygenase inhibitor caffeic acid. In order to study the role of endogenous lipoxygenase products of arachidonic acid on the chemotactic action of PDGF, effects of PDGF on the lipoxygenase pathway in smooth muscle cells were examined. Lipoxygenase products were analyzed by high-performance liquid chromatography. 15-, 5- and 12-lipoxygenase activities, in order of magnitude, were found in smooth muscle cell homogenate. However, when the lipoxygenase products were analyzed using intact cells prelabelled with [14C]arachidonic acid, only 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was found to be produced endogenously. In addition, 12-HETE was not released into the medium. Treatment of the cells with PDGF increased the endogenous production of 12-HETE. The amounts of intracellular 12-HETE in PDGF-treated cells were 126, 132 and 146% at 1, 3, and 10 hr's after the initiation of PDGF treatment, respectively, when control value at each time point was considered as 100%. Caffeic acid (10(-4) M) completely inhibited the PDGF effect on 12-HETE production. However, PDGF treatment did not significantly alter the 12-lipoxygenase activity. These results suggest that the stimulatory effect of PDGF on 12-HETE production was not mediated by the activation of 12-lipoxygenase activity. Since 12-HETE itself is a potent chemoattractant for smooth muscle cells, the present dat strongly suggest that 12-HETE could be an important intracellular mediator of the chemotactic action of PDGF on aortic smooth muscle cells.

Animals↗
PubMed1985

Measurement of immunoreactive leukotriene C4 in blood of asthmatic children.

Peptide leukotriene (LT) such as LTC4, LTD4, LTE4 have been considered to be major mediators of immediate type hypersensitivity reaction such as asthma. We have developed a rapid and simple extraction method using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay (i-LTC4). In this extraction method, 91% LTC4 was recovered in a final methanol fraction. The identity was confirmed by the recovery test and by the dilution method. The amount of i-LTC4 in plasma from asthmatic patients was determined by radioimmunoassay after the extraction. The order of the plasma level of i-LTC4 was; severe asthma greater than slight or moderate asthma greater than asthmatic patient without attack greater than healthy adult. The highest level of LTC4 was 0.27 +/- 0.11 pmol/ml in severe asthmatic plasma.

Adult↗
PubMed1985

Effect of dietary protein level on platelet aggregation in rat.

In order to investigate the effects of dietary protein level on the development of atherosclerosis and arterial thrombosis, studies were made on platelet function, plasma lipids and aortic prostaglandin I2 biosynthesis in rats. Under the same calorie intake, the group consuming a low level of protein (10% casein) increased plasma triglycerides and platelet aggregability in comparison with control (20% casein) and high protein groups (60% casein). Moreover, the low protein group produced more thromboxane A2 and less prostaglandin I2 compared with the high protein one. These data suggest that high protein diets may have beneficial effects on arterial thrombosis.

Animals↗
PubMed1985

Lipoxygenase specific inhibitors inhibit murine lymphocyte reactivity to Con A by reducing IL-2 production and its action.

Caffeic acid and AA861, specific inhibitors of lipoxygenase, reduced reactivity of murine spleen lymphocytes to Concanavalin A (Con A). They inhibited interleukin-2 (IL-2) production and its action, although they did not inhibit acquisition of lymphocyte reactivity to IL-2. Indomethacin was not able to restore the reactivity of lymphocytes to Con A even when it was combined with lipoxygenase specific inhibitors. This result suggests that lipoxygenase inhibitors exert their effects not through increasing prostaglandin E2 (PGE2) production but through inhibiting lipoxygenase. Lipoxygenase inhibitors exerted their effects even though they were removed 24 hr after the onset of culture. Taken together, these results suggest that lipoxygenase inhibitors exerted their inhibitory effects in the early period of lymphocyte activation by reducing IL-2 production and its action, implying that lipoxygenase reactions during 24 hr after stimulation may be involved in these steps.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1985

Platelet thromboxane synthesizing activity in non-insulin-dependent diabetes: correlation with diabetic retinopathy and diabetic treatment.

Since elevated thromboxane A2 synthesis could be expected to lead to microvascular injury in diabetic patients, it is important to determine the relationship between thromboxane A2 synthesis and diabetic microvascular complications. In the present study, the activity of thromboxane A2 synthesis in platelets was assessed in 57 Type 2 (non-insulin-dependent) diabetic patients by measuring the conversion of exogenously added 14C-arachidonic acid into 14C-thromboxane B2. The activity of thromboxane synthesis was significantly higher in diabetic patients than in 16 age-matched control subjects (2.61 +/- 0.07 vs 1.95 +/- 0.12 microgram . 10(9) platelets-1 . 3 min-1, respectively, p less than 0.001). When the diabetic patients were divided into three groups (nil, background, and proliferative retinopathy) on the basis of severity of diabetic retinopathy, there was a trend to increased thromboxane synthesizing activity as diabetic retinopathy develops. However, no statistically significant changes were demonstrated among these three groups. In the diabetic patients, a positive correlation was found between thromboxane synthesizing activities and glycosylated hemoglobin values (biochemical indicator of long-term glycemic control), but not between the activities and plasma glucose levels. To ascertain the effect of desirable diabetic treatment on thromboxane synthesizing activity in platelets, 9 newly diagnosed patients and 6 poorly controlled patients were examined. During treatment, all patients had declining plasma glucose and glycosylated hemoglobin levels. Thromboxane synthesizing activities in 6 patients treated by insulin decreased significantly during treatment (3.16 +/- 0.17 to 2.49 +/- 0.22 microgram . 10(9) platelets-1 .3 min-1, p less than 0.01), but 9 diabetic patients treated by diet or sulphonylureas still maintained their elevated thromboxane synthesizing activity levels (2.76 +/- 0.24 to 2.66 +/- 0.25 microgram . 10(9) platelets-1 .3 min-1,NS). These results suggest that the increased thromboxane synthesizing enzyme system is involved in the abnormal platelet function in diabetes independently of diabetic retinopathy, and that appropriate metabolic control using insulin might be successful in lowering the increased thromboxane synthesizing activity.

Aged↗
PubMed1985

Growth-coupled changes in glucosaminoglycans (heparan sulfate and hyaluronic acid) in normal and transformed human fibroblasts.

Changes in glycosaminoglycans (GAGs) were investigated in relation to cell density, growth and transformation of human fibroblasts. Relative amounts (percentages of the total GAGs) of heparan sulfate (HS) increased and those of hyaluronic acid (HA) decreased in growth-reduced (serum-starved, exogenous HS-treated and dense) cultures of normal (WI-38) cells. In contrast, transformed (WI-38 CT-1) cells exerted such GAG changes only in serum-starved cultures, but not in HS-treated or dense cultures. These results indicate that the changes in glucosaminoglycans (G1cAGs) (HS and HA) is coupled exclusively with cell growth.

Animals↗
PubMed1985

Actions of exogenous heparan sulfate and hyaluronic acid on growth and thymidine incorporation of normal and transformed human fibroblasts. A comparison with the effects of high cell density and low serum concentration and a warning against thymidine incorporation as a measure of DNA synthesis.

Treatment of normal human (WI-38) cells with exogenous heparan sulfate (HS) reduced cell growth and incorporation of radio-isotope-labeled thymidine (TdR) into DNA. In spite that growth of their transformants (WI-38 CT-1) was enhanced by HS treatment, transformed cells also decreased in TdR incorporation thereby. This peculiar observation was explained by a reduction of TdR uptake, leading to a decrease in specific radioactivity of newly synthesized DNA. The changes in cell growth and TdR incorporation by HS treatment were revealed to be similar to the changes with increasing cell density rather than by serum starvation.

Biological Transport↗
PubMed1985

Stimulatory effect of insulin on aortic smooth muscle cell migration induced by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid and its modulation by elevated extracellular glucose levels.

In investigations on the role of insulin on migration of rat aortic smooth muscle cells, migration of the cells was measured by a modified Boyden chamber technique with 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) as a chemoattractant. Insulin itself was not a chemoattractant for these cells, and insulin added just before the migration assay did not affect cell migration in the presence or absence of 12-HETE. Cells pretreated with insulin in culture dishes for a long period, however, showed a significant increase in migration induced by 12-HET, and the increase depended on the insulin concentration: concentrations of insulin of greater than 50 microIU/ml caused about twofold increase in cell migration. On the other hand, long-term incubation with various concentrations of insulin (0.15-1000 microIU/ml) did not affect nonspecific cell migration in the absence of 12-HETE. The stimulatory effect of insulin on cell migration gradually increased with the duration of insulin treatment, reaching a plateau after 4 days. Thus, insulin stimulated 12-HETE-induced smooth muscle cell migration in a time- and dose-dependent manner. When the extracellular D-glucose concentration in the Boyden chamber was increased from 100 to 300 mg/dl, the stimulatory effect of insulin on 12-HETE-induced cell migration was augmented. This modulation by D-glucose was not due to an increase in the osmotic pressure of the medium, since addition of mannitol to increase the osmotic pressure did not enhance the effect of insulin on cell migration.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗