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Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 577 records · Page 32Linked to original sources
PubMed1984

Inhibition by palmitoylcarnitine of adhesion and morphological changes in HL-60 cells induced by 12-O-tetradecanoylphorbol-13-acetate.

Effects of DL-palmitoylcarnitine (PC), an inhibitor of calciumactivated, phospholipid-dependent protein kinase (protein kinase C), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell differentiation were investigated in human promyelocytic leukemia cells (HL-60). TPA caused HL-60 cell adhesion concomitant with morphological changes, and an increase in acid phosphatase activity. The median effective concentration was 1 nM, which corresponded well to the dissociation constant of [3H]TPA binding to the cell extract. [3H]TPA binding to the cell extract was saturable and reversible. The maximal number of [3H]TPA-binding sites was 1.5 pmol/mg protein and a Hill coefficient was unity, indicating noncooperative interactions. PC, but neither palmitic acid nor DL-carnitine, inhibited the TPA-induced cell adhesion and morphological changes with the median inhibitory concentration of 1 microM, whereas a TPA-induced increase in acid phosphatase activity was not affected by 3 microM PC. Addition of PC 1 or 2 days after the addition of TPA was also effective in inhibiting the cell adhesion. Among various acylcarnitines, PC had the largest effect. [3H]TPA binding to the cell extract was not inhibited by PC at the concentration which was effective in inhibiting the TPA-induced cell adhesion. These results indicate that protein kinase C possibly mediates HL-60 cell differentiation induced by TPA.

Caenorhabditis elegans Proteins↗
PubMed1984

Effects of flavonoids and antioxidants on 12-O-tetradecanoyl-phorbol-13-acetate-caused epidermal ornithine decarboxylase induction and tumor promotion in relation to lipoxygenase inhibition by these compounds.

The effects of flavonoids, antioxidants and related compounds on 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused epidermal ornithine decarboxylase (ODC) induction, DNA synthesis and skin tumor promotion, and on epidermal lipoxygenase activity, were investigated using CD-1 mice. Morin, fisetin , kaempferol and n-propyl gallate potently inhibited epidermal lipoxygenase activity, and esculetin , butylated hydroxyanisole (BHA), alpha-naphthol and 2,3- dihydroxynaphthalene (2,3- DHNA ) moderately inhibited it. alpha-Tocopherol, (+)catechin, (-) epicatechin and butylated hydroxytoluene (BHT) were inactive. Similarly, morin, fisetin , kaempferol and n-propyl gallate markedly inhibited TPA-caused ODC induction. Esculetin , BHA, alpha-naphthol, 2,3- DHNA and alpha-tocopherol inhibited it less potently, but significantly. (+)Catechin, (-) epicatechin and BHT failed to inhibit or only slightly inhibited TPA-caused ODC induction. TPA-caused DNA synthesis was not inhibited by morin, esculetin , (+)-catechin or alpha-tocopherol. The TPA-induced skin tumor promotion was markedly inhibited by morin and slightly suppressed by esculetin and alpha-tocopherol, but (+)-catechin was inactive. Thus, the inhibitory effects of flavonoids and antioxidants on the TPA-caused ODC induction and tumor promotion were roughly parallel with their activities of lipoxygenase inhibition. These results further support our hypothesis that a lipoxygenase product(s) is involved in the mechanism of TPA-caused ODC induction and tumor promotion.

Animals↗
PubMed1984

Participation of cytochrome P-450 in reductive metabolism of 1-nitropyrene by rat liver microsomes.

Reductive metabolism of carcinogenic 1-nitropyrene by rat liver microsomes and reconstituted cytochrome P-450 systems was investigated. Under the nitrogen atmosphere, 1-aminopyrene was the only detected metabolite of 1-nitropyrene. The reductase activity in liver 105,000 X g supernatant fraction was ascribed to DT-diaphorase, aldehyde oxidase, and other unknown enzyme(s) from the results of cofactor requirements and inhibition experiments. The microsomal reductase activity was inhibited by oxygen, carbon monoxide, 2,4-dichloro-6-phenylphenoxyethylamine, and n-octylamine. Flavin mononucleotide markedly enhanced the activity, and 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride also enhanced it, but slightly. The microsomal activity was induced by the pretreatment of rats with 3-methylcholanthrene, sodium phenobarbital, or polychlorinated biphenyl, and the increments of the activity correlated well with those of the specific contents of cytochrome P-450 in microsomes. The reductase activity could be reconstituted by NADPH-cytochrome P-450 reductase and forms of cytochrome P-450 purified from liver microsomes of polychlorinated biphenyl-induced rats. Among four forms of cytochrome P-450 examined, an isozyme P-448-IId which showed high activity in hydroxylation of benzo(a)pyrene catalyzed most efficiently the reduction of 1-nitropyrene. The results of this study indicate the central role of cytochrome P-450 in the reductive metabolism of 1-nitropyrene in liver microsomes.

Animals↗
PubMed1984

[Effects of heart rate on body surface potential distribution in patients with atrial pacemaker].

Nine patients of sick sinus syndrome with atrial programmable pacemaker (3 males and 6 females, aged from 53 to 72 years) were studied to assess the effect of heart rate on the body surface potential distribution. Body surface maps (87 lead points) and M-mode echocardiograms were recorded at 20-beat increments of heart rate from 60 to 140 beats/min during atrial pacing. The potential changes of R and S voltages were evaluated quantitatively and were correlated with the changes of echocardiographically measured left ventricular dimension. As the heart rate increased, left ventricular dimension in end-diastole (LVDd) decreased gradually (Table 1), and a significant decrease was observed when the heart rate increased from 80 to 100 beats/min and from 100 to 120 beats/min, respectively, (p less than 0.05). With a decrease in LVDd, the distance between the left ventricular posterior wall and the anterior chest wall decreased and the left ventricular wall increased in its thickness. These changes, however, were not statistically significant. With an increase in the heart rate, R voltages decreased gradually in the left lateral chest and the sum of R voltages (sigma R) of six lead points in the left lateral chest including leads V5-6 decreased significantly when the heart rate increased from 60 to 100 beats/min and from 80 to 120 beats/min, respectively (p less than 0.02) (Table 2). On the other hand, R voltages remained unchanged in the left anterior chest during atrial pacing, then the sum of R voltages of six lead points in the left anterior chest including leads V2-4 and the sum of R voltages of 87 lead points did not show any significant changes (Table 2). An increase in the absolute value of S voltages was observed in the left anterior chest and the sum of S voltages of six lead points in the left anterior chest including leads V2-4 increased when the heart rate increased from 60 to 100 beats/min and from 80 to 120 beats/min, respectively (p less than 0.1) (Table 3) A decrease of R voltages in the left lateral chest was consistent with the reduction in LVDd (p less than 0.005). It is concluded that the changes in body surface QRS amplitudes during atrial pacing are related to those in the left ventricular dimension and that R voltages in the left lateral chest are fairly sensitive to see the changes in LVDd in cases with no abnormal wall motion of the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1983

Insulinotropic effect of the tumor promoter teleocidin in isolated pancreatic islets.

A tumor promoter teleocidin induced insulin secretion from isolated pancreatic islets in a concentration-dependent manner. The teleocidin-induced secretion was inhibited by p-bromophenacyl bromide, nordihydroguaiaretic acid, 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone, but not by indomethacin. Insulinotropic concentrations of teleocidin stimulated 6-keto-prostaglandin F1 alpha release from pancreatic islets. These results suggest that phospholipase A2 activation and lipoxygenase product(s) are involved in the mechanism of teleocidin-induced insulin secretion.

Alkaloids↗
PubMed1983

Effects of W-7 on catecholamine release and 45Ca2+ uptake in cultured adrenal chromaffin cells.

Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, on catecholamine (CA) release and 45Ca2+ uptake were studied using cultured bovine adrenal chromaffin cells. W-7 inhibited the carbamylcholine (CCh)-evoked CA release and 45Ca2+ uptake in a concentration-dependent manner. The inhibitory effect of W-7 on CCh-evoked CA release was not overcome either by an increase in extracellular calcium or CCh concentration. Although W-7 inhibited the high K+-evoked CA release and 45Ca2+ uptake, potency of the drug was approximately 50-100 fold less than when inhibiting the CCh-evoked CA release and 45Ca2+ uptake. The inhibitory effects of W-7 were observed both in norepinephrine release and epinephrine release. Moreover, W-7 inhibited the CCh-evoked 45Ca2+ efflux. These results suggest that the inhibition of CA release by W-7 in adrenal chromaffin cells is mainly due to its inhibition of calcium uptake. W-7 may influence the linkage between acetylcholine-receptor and calcium uptake with higher potency than depolarization-dependent calcium entry.

Adrenal Medulla↗
PubMed1983

Developmental changes in the effect of morphine, epinephrine and carbachol on plasma cyclic nucleotide level in rats.

The developmental changes in the effects of morphine, FK 33-824, a synthetic opioid peptide, epinephrine and carbachol on the plasma cyclic AMP and GMP level were investigated in rats ranging in age from 1 to 49 days. The effect of morphine in elevating plasma cyclic AMP and GMP level increased with age with a peak at day 21. The effect of FK 33-824 followed a similar developmental course of that of morphine except at day 49. Epinephrine and carbachol increased the plasma cyclic AMP level even in one-day old rats. The increase in plasma cyclic GMP induced by carbachol increased with age, peaked at day 14, then declined until day 49. These results suggest that the delay in advent of the effect of opioids on plasma cyclic nucleotides in the early neonatal period is mainly due to the slow development of opioid receptors in the brain.

Aging↗
PubMed1983

Modulation of insulin secretion by lipoxygenase products of arachidonic acid. Relation to lipoxygenase activity of pancreatic islets.

Glucose (16.7 mM)-induced insulin secretion from isolated pancreatic islets of rats was inhibited by nordihydroguaiaretic acid (NDGA), 1-phenyl-3-pyrazolidinone (phenidone), 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline (BW755C), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 2,6-di-tert-butyl-4-methylphenol (BHT). Indomethacin and aspirin, however, failed to inhibit the glucose-induced insulin secretion but rather tended to enhance it. The glucose-induced insulin secretion was inhibited by 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) (50 microM), 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) (100 microM), and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) (100 microM), but not by 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) (100 microM). Exogenous 5-HETE (10 microM) induced significant insulin secretion in a low glucose (3.3 mM) medium. Racemic 5-HETE also showed insulinotropic effect in a concentration-dependent manner with the concentrations 20 microM or above, whereas 12-HETE, 15-HETE, 15-HPETE, 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid, 5-hydroxy-6-glutathionyl-7,9,11,14-eicosatetraenoic acid, 5-hydroxy-6-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid, prostaglandin E2, and prostaglandin F2 alpha failed to induce insulin secretion. Although significant insulin release was observed with arachidonic acid (greater than or equal to 100 microM), reduce cell viability was evident at 200 microM. When the 10,000 X g supernatant of isolated pancreatic islet homogenate was incubated with [3H]arachidonic acid at 37 degrees C in the presence of GSH and Ca2+, and the labeled metabolites then extracted with ethyl acetate and subjected to reverse phase high pressure liquid chromatography, several radioactive peaks, coeluted with authentic 15-, 12-, and 5-HETE, were observed. The radioactive peaks were completely suppressed by the addition of either NDGA, BW755C, or phenidone into the medium. The results support our contention i.e. the involvement of lipoxygenase product(s) in the secretory mechanism of insulin, and further suggest that 5-lipoxygenase system may play a role.

Animals↗
PubMed1983

Mechanism of activation of proximate mutagens in Ames' tester strains: the acetyl-CoA dependent enzyme in Salmonella typhimurium TA98 deficient in TA98/1,8-DNP6 catalyzes DNA-binding as the cause of mutagenicity.

The mechanism of activation of proximate mutagens in Ames' tester strains was described. 2-Hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) and 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were activated to DNA-binding species in the presence of acetyl-CoA by the enzyme(s) in Salmonella typhimurium TA98, and this enzyme was deficient in TA98/1,8-DNP6. Mutagenicity of N-OH-Glu-P-1 to TA98/1,8-DNP6 was much lower than that to TA98. Therefore, it was demonstrated that the acetyl-CoA dependent enzyme(s) activated N-OH-Glu-P-1 to the active form which could covalently bind to DNA and subsequently caused mutagenicity.

Acetyl Coenzyme A↗
PubMed1983

A high spin form of cytochrome P-448 highly purified from PCB-treated rats--II. Characteristic requirement of cytochrome b5 for maximum activity.

A high spin form of cytochrome P-448 (PCB P-448-H), highly purified from microsomes of PCB-treated rats, catalyzed oxidations of several compounds and required cytochrome b5 for its full activities in all oxidations examined. PCB P-448-H catalyzed the hydroxylation of aniline and O-dealkylations of p-alkoxy derivatives of aniline and nitrobenzene and 7-alkoxy derivatives of coumarin. Among the activities measured, hydroxylation of aniline and O-dealkylation of p-alkoxy derivatives of aniline were catalyzed by PCB P-448-H more efficiently than by PCB P-448-L, which was a low spin form of cytochrome P-448 purified from liver microsomes of PCB-treated rats. In all reactions, PCB P-448-H required cytochrome b5 for maximum activity. Slight requirements were also seen with PCB P-448-L but varied equivocally depending on the substrates. Cytochrome b5 showed its maximum effects on p-propoxyaniline O-depropylation activity at a molar ratio of cytochrome b5 to PCB P-448-H of 1:2. The enhancement by cytochrome b5 was more pronounced when lower concentrations of either the substrate or NADPH-cytochrome P-450 reductase were added to the reconstituted system. Based on these results, we confirm that PCB P-448-H is a unique form of cytochrome P-448 with respect to the requirements for cytochrome b5 and is a good probe to study the mechanisms involved in the enhancement of drug oxidations by cytochrome b5.

Animals↗
PubMed1983

Stimulation of 6-keto-prostaglandin F1 alpha release from isolated pancreatic islets by an insulinotropic concentration of glucose.

In a glucose-free medium, the release of 6-keto-prostaglandin F1 alpha from isolated pancreatic islets was 1.67 pg/islet/60 min. The release was not altered by increasing the glucose concentration to 3.3 mM, whereas the release was significantly increased to 3.79 pg/islet/60 min by 16.7 mM glucose. Indomethacin (10 microM) and mepacrine (100 microM) markedly suppressed the 6-keto-prostaglandin F1 alpha release. The results indicate that the insulinotropic concentration of glucose enhances the enzymatic formation of 6-keto-prostaglandin F1 alpha in pancreatic islets. It seems highly possible that glucose enhances 6-keto-prostaglandin F1 alpha formation by stimulating phospholipase A2 in pancreatic islets.

6-Ketoprostaglandin F1 alpha↗