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T Tatsuno

Publications and source records attributed to T Tatsuno.

At least 55 records · Page 3Linked to original sources
PubMed1984

Caffeic acid is a selective inhibitor for leukotriene biosynthesis.

.eukotrienes are significantly involved in immunoregulation and in a variety of diseases, including asthma, inflammation and various allergic conditions. They are initially biosynthesized by 5-lipoxygenase from arachidonic acid, which can also be metabolized to prostaglandin endoperoxide by cyclooxygenase. The specific inhibitors for 5-lipoxygenase would be useful not only as tools for investigating the regulation mechanism of leukotriene biosynthesis, but also as drugs for clinical use. Although recently a few selective inhibitors have been reported, most of them are difficult to obtain, since they are new compounds. We found that caffeic acid, which is one of the most common reagents, is a selective inhibitor for 5-lipoxygenase and therefore for leukotriene biosynthesis. The inhibitory effect of its methyl ester on 5-lipoxygenase (ID50 = 4.8 X 10(-7) M) was stronger than that of caffeic acid itself (ID50 = 3.7 X 10(-6) M). Caffeic acid inhibited 5-lipoxygenase in a non-competitive manner. Caffeic acid and its methyl ester did not inhibit prostaglandin synthase activity at all, at least up to 5 X 10(-4) M, but rather stimulate at higher doses. The biosynthesis of leukotriene C4 and D4 in mouse mast tumor cells was also inhibited completely with 10(-4) caffeic acid. Besides, caffeic acid had little effect on arachidonic acid metabolism in platelet at less than 1 X 10(-5) M, but at higher doses it showed a definite inhibitory effect, i.e., thromboxane B2, HHT (12(S)-hydroxy-5,8,10-heptadecatetraenoic acid) and 12-HETE (12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid) syntheses were inhibited 33, 40 and 80% at 1 X 10(-4) M, respectively. Platelet aggregation induced by arachidonic acid was also inhibited by caffeic acid at high dose, while platelet aggregation induced by ADP is not influenced by caffeic acid at all. The observations on caffeic acid and its derivatives may contribute to leukotriene research.

Animals↗
PubMed1984

Liver injuries induced by cyclochlorotine isolated from Penicillium islandicum.

Sequential morphological changes in murine liver induced by cyclochlorotine (CC), a secondary metabolite of Penicillium islandicum were investigated by transmission electron microscopy and scanning electron microscopy. Within 15 min after the administration of CC there was a marked dilatation of Disse's space around the portal triads, and the exudates then poured out into the space which was formed by the invagination of the hepatocyte plasma membrane. Shortly after the invagination was completed, the connection between Disse's space and the invaginated space was pinched off, so that this space became a membrane-bound vacuole. After dehydration, the vacuoles became granular. The liver injuries induced by CC were influenced by various pretreatments. The results indicate that drug-metabolizing systems mediated by cytochrome p-450 in the hepatocytes may play an important role in the hepatotoxicity of CC.

Aging↗
PubMed1984

Synthesis of phosphotriester by DCC and its biological activities.

The synthesis of a phosphotriester, an inhibitor of acetylcholinesterase, was performed by the coupling reaction of diethylphosphate with various phenolic compounds using dicyclohexylcarbodiimide (DCC). All of the compounds synthesized inhibited housefly acetylcholinesterase activity. Derivatives including an electronegative part as a nitro group in the phenol ring showed strong inhibition towards housefly acetylcholinesterase, but those with hydrophobic derivatives of the phenol group, such as cresol, naphthol and biphenol, showed relatively low inhibition. In experiments with housefly, the value of LD50 for each chemical correlated with the I50 value for acetylcholinesterase except alpha-naphthyl diethylphosphate, beta-naphthyl diethylphosphate and p,p'-biphenyl diethylphosphate.

Acetylcholinesterase↗
PubMed1984

Modulation by unsaturated fatty acids of norepinephrine- and adenosine-induced formation of cyclic AMP in brain slices.

The effect of linoleic acid on the formation of cyclic AMP in the slices of guinea pig cerebral cortex was examined. Treatment of the slices with linoleic acid resulted in an increase of basal and of norepinephrine-stimulated formation of cyclic AMP. The stimulatory effect on the basal level of cyclic AMP was not specific for linoleic acid: the potency of the fatty acid was related to the magnitude of unsaturation. In contrast, the enhancement of norepinephrine-stimulated formation of cyclic AMP seemed relatively specific for linoleic acid and arachidonic acid. Linoleic acid markedly enhanced the stimulated formation of cyclic AMP by histamine and adenosine, as well that by norepinephrine, without affecting that by excitatory amino acids and veratridine. Theophylline, adenosine deaminase, and 2'-deoxyadenosine antagonized the effect of linoleic acid. Linoleic acid enhanced the maximum responses to norepinephrine and adenosine without altering the ED50 values for these agonists. When linoleic acid-treated slices were washed with Krebs-Ringer containing defatted bovine serum albumin, both enhancement of the response to norepinephrine and the amount of [14C]linoleic acid incorporated in a free form significantly diminished.

Adenosine↗
PubMed1983

Selective inhibition of 5-lipoxygenase by natural compounds isolated from Chinese plants, Artemisia rubripes Nakai.

Three of four natural compounds, which are caffeic acid, eupatilin and 4'-demethyleupatilin, isolated from Chinese plant, Artemisia rubripes Nakai selectively inhibited 5-lipoxygenase of cultured mastocytoma cells. Half-inhibition doses (ID50) for caffeic acid, eupatilin and 4'-demethyleupatilin were 3.7, 14 and 18 X 10(-6) M, respectively. The inhibition by caffeic acid was non-competitive types. Prostaglandin synthase activities were little inhibited by eupatilin and 4'-demethyleupatilin, but rather stimulated by caffeic acid. The formation of leukotriene C4 and D4 by mast tumor cells was almost completely suppressed by these compounds at 10(-4) M.

Animals↗
PubMed1983

Mechanism of the mRNA guanylyltransferase reaction: isolation of N epsilon-phospholysine and GMP (5' leads to N epsilon) lysine from the guanylyl-enzyme intermediate.

The mRNA capping reaction catalyzed by rat liver mRNA guanylyltransferase proceeds through an enzyme-GMP intermediate in which GMP is linked to the enzyme by a phosphoamide linkage. The studies described here show that GMP is bound to the epsilon-amino group of lysine of rat liver guanylyltransferase. The enzyme-[32P]GMP intermediate was digested with pronase to a [32P]GMP-peptide which was then converted to [32P]phosphoryl-peptide through periodate oxidation followed by beta-elimination. After alkaline hydrolysis of the [32P]phosphoryl-peptide, the major radioactive product co-electrophoresed with the authentic N epsilon-phospholysine on DEAE-cellulose paper. Neither [32P]Nimid-phosphohistidine nor Nguanido-phosphoarginine was detected in the hydrolysates. Furthermore, formation of N epsilon-guanylyl-lysine linkage on the enzyme was more directly shown by isolation of [32P]GMP(5' leads to N epsilon)lysine when the steps of periodate oxidation and beta-elimination were omitted. The results indicate that the nucleophile in the guanylyltransferase to which the guanylyl residue is linked is the epsilon-amino group of a lysine residue. [32P]Phosphoryl-lysine was also isolated from the vaccinia virus capping enzyme-[32P]GMP intermediate. Guanylyltransferase from HeLa cells, wheat germ, Artemia salina and yeast also formed the enzyme-GMP complex and, from the stability of the complex, the linkage between the enzyme and GMP was suggested to be a phosphoamide.

Animals↗
PubMed1982

Cysteine sulfinic acid in the central nervous system: antagonistic effect of taurine on cysteine sulfinic acid-stimulated formation of cyclic AMP in guinea pig hippocampal slices.

The stimulatory effect of cysteine sulfinic acid on cyclic AMP formation was examined in slices from three different regions of guinea pig brain. The inhibitory effect of taurine on the stimulated formation of cyclic AMP was also studied. Cysteine sulfinic acid (1--10 mM) greatly increased the cyclic AMP level in striatal, cortical, and especially hippocampal slices. In hippocampal slices, taurine (0.1--30 mM) markedly lowered the increase of cyclic AMP induced by cysteine sulfinic acid, but not that induced by glutamate or aspartate. In this region, taurine also reduced the stimulatory effects on cyclic AMP formation of adenosine, norepinephrine, and histamine, but not of depolarizing agents. It did not, however, inhibit the effects of any of these stimulants in cortical slices. These results suggest that sulfur-containing amino acids, such as cysteine sulfinic acid and taurine, regulate the cyclic AMP level in the hippocampus.

Animals↗
PubMed1982

Induction of suppressor macrophages in mice by Fusarenon-X.

Intraperitoneal injection of Fusarenon-X into BALB/c mice, a mycotoxin produced by Fusarium nivale Fn 2B, depressed polyclonal antibody formation of splenic lymphocytes in response to pokeweed mitogen (PWM). This inhibitory activity was found to reside in the surface immunoglobulin-negative spleen cell fraction of Fusarenon-X-treated mice, sIg-(FX), which comprised mainly T lymphocytes and smaller number of non-lymphocytic cellular elements. However, reconstitution experiments for in vitro antibody formation provided evidence that T lymphocytes from Fusarenon-X-treated mice, T(FX), which were separated from non-lymphocytic cells by use of carbonyl iron/magnet, were as effective as T lymphocytes from normal mice, T(N), in supporting antibody formation. Furthermore, addition of non-lymphocytic cells, NL(FX), or adherent cells, AD(FX), prepared from spleen cells of Fusarenon-X-treated mice to normal spleen cells strongly inhibited in vitro antibody formation against PWM or a bacterial lipopolysaccharide (LPS). These results strongly indicated that Fusarenon-X induced non-lymphocytic suppressor cells in the spleen of the treated mice which had features in common with activated macrophages.

Animals↗
PubMed1982

Immunosuppressive effect of a trichothecene mycotoxin, Fusarenon-X in mice.

The in vitro treatment with Fusarenon-X, a mycotoxin produced by Fusarium nivale Fn 2B, depressed the mitogenic responses of mouse lymphocytes to the T-cell mitogens, phytohaemagglutinin (PHA) and concanavalin A (Con A), but to a lesser extent to B-cell mitogen, a bacterial lypopolysaccharide (LPS). The in vitro treatment of mice with Fusarenon-X also decreased the responsiveness of splenic lymphocytes to the T-cell mitogen, Con A. Administration of Fusarenon-X to BALB/c mice before immunization significantly reduced anti-DNP IgE and IgG1 responses, while the treatment of mice after immunization was less effective. The number of spleen cells of the treated mice was increased with a reduction of T lymphocytes and an increase of granulocytic elements. In vitro antibody responses of spleen cells from Fusarenon-X treated mice by pokeweed mitogen (PWM) or LPS were also suppressed. Reconstruction experiments using sIg positive and negative spleen cells from normal and Fusarenon-X treated mice showed that this inhibitory effect resided in the sIg negative cell population.

Animals↗
PubMed1981

Activation of adenylate cyclase of rat brain by lipid peroxidation.

The relationship between adenylate cyclase activity in the synaptic membrane fraction (M1) of rat brain and lipid peroxidation of these membranes was examined. In the presence of 5 mM dithiothreitol (DTT), 1 to 10 microM Fe/+ activated adenylate cyclase 2- to 4-fold. Of several metal ions, Fe2+ was the most effective. Other enzymes in M1, such as Mg2+-ATPase, (Na+-K+)-ATPase, 5'-nucleotidase, acetylcholinesterase, and phosphodiesterase, were not activated by Fe2+ plus DTT. Activation of adenylate cyclase by Fe2+ plus DTT was accompanied by production of malondialdehyde, a product of lipid peroxidation. Formation of malondialdehyde was completely parallel with enzyme activation. Ascorbic acid or a NADPH system also stimulated enzyme activity and caused lipid peroxidation. Activation of the enzyme and lipid peroxidation induced by Fe2+ plus DTT, ascorbic acid, or NADPH was completely prevented by simultaneous addition of N,N'-diphenyl-p-phenylenediamine, an inhibitor of lipid peroxidation. This inhibitor also prevented the decrease in turbidity of the enzyme preparation induced by Fe2+ plus DTT. The stimulatory effects of NaF, guanylyl-5'-imidodiphosphate and calmodulin, respectively, and that of Fe2+ plus DTT on the enzyme activity were additive. Activation of adenylate cyclase by Fe2+ plus DTT was only observed in brain synaptic membranes, not in erythrocyte ghosts, liver plasma membranes, or cardiac sarcolemma. These results indicate that lipid peroxidation of synaptic membranes was accompanied by specific stimulation of adenylate cyclase activity.

Adenosine Triphosphate↗