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T Satoh

Publications and source records attributed to T Satoh.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin 2-induced activation of Ras requires two domains of interleukin 2 receptor beta subunit, the essential region for growth stimulation and Lck-binding domain.

Interleukin 2 (IL-2) can stimulate the proliferation of various kinds of T-cell lines. The receptor for IL-2 is composed of at least two subunits (alpha and beta), of which beta subunit plays the major role in transducing growth signals into the cells. A nonreceptor-type tyrosine kinase, Lck, is associated with IL-2 receptor beta subunit, and the binding of IL-2 to its receptor induces the activation of Lck. On the other hand, it has been shown that stimulation of T-cells with IL-2 causes rapid activation of Ras protein. In this paper, we describe that both of the two regions in IL-2 receptor beta subunit, the indispensable region for the induction of cell growth (serine-rich region) and the binding region of Lck protein (acidic region), are required for the activation of Ras. These two regions are also required for tyrosine phosphorylation of an 85-kDa cellular protein (p85) and the accumulation of fos and jun mRNAs. This observation suggests also that the activation of a receptor-associated tyrosine kinase in response to IL-2-stimulation is primarily responsible for subsequent activation of the pathway through Ras to Fos and Jun.

Animals↗
PubMed1992

Differentiation factors, including nerve growth factor, fibroblast growth factor, and interleukin-6, induce an accumulation of an active Ras.GTP complex in rat pheochromocytoma PC12 cells.

Ras has been thought to be involved in neuronal differentiation of rat pheochromocytoma PC12 cells. PC12 cells are immature adrenal chromaffin-like cells which undergo differentiation to sympathetic neuron-like cells in response to nerve growth factor (NGF). Fibroblast growth factor (FGF) and interleukin (IL)-6 can also induce differentiation of PC12 cells. In this paper, we report that NGF, FGF, and IL-6 induce an accumulation of an active Ras.GTP complex. In the serum-starved culture of PC12 cells, 6% of the Ras protein was complexed with GTP. Upon stimulation with NGF, the percentage of Ras.GTP increased to 24% after 2 min, and the high level of Ras.GTP was maintained for at least 16 h. On the other hand, the activation of Ras by FGF and IL-6 showed distinct kinetics; about 3-fold increase of Ras.GTP was detected at 10 min, and afterward, the level returned to the basal level within 60 min. These observations provide direct evidence that activation of Ras is involved in signal transduction from these differentiation factors. In addition, it was found that growth factors, including epidermal growth factor, insulin, and insulin-like growth factor-I, and a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), can also activate Ras under the same conditions. A tyrosine kinase-specific inhibitor, genistein, inhibited the increase of Ras.GTP induced by NGF and other factors. On the other hand, down-regulation of protein kinase C (PKC) by prolonged treatment with TPA, which sufficiently blocked TPA-induced Ras activation, did not abolish the formation of Ras.GTP by NGF. These results suggest that tyrosine kinases rather than PKC play a major role in the NGF-induced activation of Ras in PC12 cells.

Animals↗
PubMed1992

Molecular cloning and characterization of genes encoding rat pancreatic cholecystokinin (CCK)-releasing peptide (monitor peptide) and pancreatic secretory trypsin inhibitor (PSTI).

The genes encoding a rat pancreatic cholecystokinin (CCK)-releasing peptide (monitor peptide) and its structurally related peptide, rat pancreatic secretory trypsin inhibitor (PSTI), have been isolated and sequenced. The two genes share extremely high sequence similarity in the 5' flanking regions, suggesting that these regions may be responsible for the characteristic coordinate expression of the two peptides.

Amino Acid Sequence↗
PubMed1992

Molecular modelling of the structures of endothelin antagonists. Identification of a possible structural determinant for ET-A receptor binding.

Computer-aided molecular modelling of the endothelin (ET-A) receptor antagonists, BQ-123 and BE-18257B, shows that they have very similar 3D structures. Parts of their 3D structures are also shown to match closely with that reported for residues 6-8 in endothelin-1. On the basis of these similarities (and with supporting evidence from literature data on endothelin structure-activity relationships) a structural determinant is proposed for ET-A receptor binding, and novel designs of peptide are suggested for providing more potent and selective ET-A receptor antagonists.

Amino Acid Sequence↗
PubMed1992

3-O-alkylascorbic acids as free radical quenchers. 3. Protective effect on coronary occlusion-reperfusion induced arrhythmias in anesthetized rats.

Structural modification of ascorbic acid by substitution of the 3-hydroxy group with lipophilic moieties has allowed the development of agents for treating reperfusion injury. These ascorbic acid derivatives inhibited lipid peroxidation, and some of them also reduced coronary reperfusion-induced arrhythmias in anesthetized rats. We found that 3-O-[(dodecylcarbonyl)methyl]ascorbic acid (8) was protective against reperfusion injury without directly influencing hemodynamics. 2-O-Octadecylascorbic acid (19) and 5,6-O-dodecylideneascorbic acid (15) also exhibited a marked effect on reperfusion injury, but significantly reduced the arterial blood pressure and heart rate in rats.

Anesthesia↗
PubMed1992

Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells).

We studied the effect of thyroid status on thyrotropin-releasing hormone receptor (TRH-R) mRNA levels both in vivo and in vitro (GH3 cells) using a cloned rat TRH-R cDNA by RT-PCR. Experimental hypothyroid rats were produced by total thyroidectomy and were then killed 7 days after the operation. TRH receptor binding in the anterior pituitary and serum TSH level were elevated approximately 2-fold and 8-fold, respectively, in 7 day thyroidectomized rats. TRH-R mRNA levels in hypothyroid rats were also increased significantly compared with those of normal rats. In GH3 cells, however, no significant change of TRH-R mRNA level was observed between cultures treated with triiodothyronine (T3, 10(-9) and 10(-7) M) and the untreated group. The present data indicate that 1) the in vivo effects of thyroid status on TRH-R mRNA levels differ from the in vitro one, and that 2) the down regulation of TRH-R binding by thyroid hormone in GH3 cells may be mediated by translational or post-translational mechanisms.

Amino Acid Sequence↗
PubMed1992

Developmental aspects of a unique glutathione S-transferase subunit Yx in the liver cytosol from rats with hereditary hyperbilirubinuria. Comparison with rat fetal liver transferase subunit Yfetus.

The unique glutathione S-transferase (GST) subunit Yx, which is undetectable in normal adult rat liver cytosol, was shown to occur in the liver cytosol of rats with hereditary hyperbilirubinuria (EHB). The Yx subunit is a member of the Alpha-class GST subunits, and is immunologically closely related to the Yc subunit. The Yx subunit has an apparent M(r) of 26,400, different from those of Ya (M(r) 25,800), Yb1 and Yb2 (both M(r) 27,200) and Yc (M(r) 28,400). During postnatal development in livers of EHB rats, the Yx subunit concentration in either sex was highest during the first week post partum and declined rapidly with age. Although the concentration of subunit Yx at 8 weeks of age accounted for about 60% in females and 40% in males of that observed in 1-week-old 'neonatal' male EHB rats, concentrations in females thereafter increased gradually to almost the neonatal level and remained at this high level at least up to 37 weeks of age, whereas the concentration in males did not increase again. Thus the post-pubertal Yx subunit concentration was 2-fold higher in females than in males. In contrast, in normal Sprague-Dawley rat liver, the Yfetus subunit, with the same M(r) as the Yx subunit, had the highest concentration in 10-day-old animals, declined rapidly thereafter, and was not detectable in the post-pubertal period. The Yfetus subunit was also immunoreactive with an antibody against GST YcYc. The analysis of GST subunits by reverse-phase h.p.l.c. revealed that the Yx subunit was eluted at a retention time different from other known subunits, but coincided with that of Yfetus. The N-terminal amino acid sequence of the Yx subunit displayed a high degree of sequence similarity to that of the Yfetus subunit. These data suggest that the Yx subunit in EHB rats may be very similar to, if not identical with, the Yfetus subunit.

Amino Acid Sequence↗
PubMed1992

Inhibition of interleukin 3 and granulocyte-macrophage colony-stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases.

Interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the proliferation of several kinds of cultured hematopoietic cell lines. Growth signals from IL-3 and GM-CSF cause accumulation of active Ras.GTP complexes in PT18 mouse mast cell line (Satoh, T., Nakafuku, M., Miyajima, A., and Kaziro, Y. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 3314-3318). In this paper we describe the effect of herbimycin A, a tyrosine kinase-specific inhibitor, on the activation of Ras. The increase of Ras.GTP induced by IL-3 and GM-CSF diminished in cells treated with 0.5 approximately 1 micrograms/ml of herbimycin A for 24 h prior to the addition of the growth factors. Under this condition, the extent of phosphorylation on tyrosine residues of proteins decreased. However, the activity of cAMP-dependent protein kinase and protein kinase C did not change. Growth of cells in the presence of IL-3 or GM-CSF was also completely inhibited. These observations suggest that tyrosine kinases are involved in the pathways between IL-3 and GM-CSF receptors and Ras and that they are essential for the growth stimulated by these growth factors.

Animals↗
PubMed1992

Prolonged decrease of serum calcium concentration by murine gamma-interferon in hypercalcemic, human tumor (EC-GI)-bearing nude mice.

Murine gamma-interferon (MuIFN-gamma) is a potent inhibitor of bone resorption induced by interleukin 1 and parathyroid hormone-related protein in vitro. To investigate whether MuIFN-gamma is also effective in vivo, the cytokine was injected s.c. into hypercalcemic, tumor (EC-GI)-bearing nude mice, in which parathyroid hormone-related protein and interleukin 1 alpha are synergistically responsible for causing humoral hypercalcemia. When MuIFN-gamma was injected s.c. at a dose of 1 to 20 x 10(4) units for 5 days consecutively, serum calcium concentrations in the tumor-bearing mice decreased in a dose-dependent manner. The minimal effective dose was 5 x 10(4) units/mouse. Unlike calcitonin, which decreased the serum calcium concentration for only 1 to 2 days despite continuous daily injections, MuIFN-gamma decreased it for more than 7 days even after the injections had been stopped. Human gamma-interferon was completely ineffective. The decrease in serum calcium concentration was accompanied by a decrease in urinary calcium excretion. Histological examination of the femur revealed a decreased number of osteoclasts in the MuIFN-gamma-treated mice. Furthermore, MuIFN-gamma, when injected into nude mice or normal mice at a dose of 15 x 10(4) units for 3 days, almost completely abolished the formation of multinucleated osteoclast-like cells in vitro. These findings suggest that MuIFN-gamma suppresses the formation and maturation of osteoclasts and inhibits osteoclastic bone resorption, resulting in the prolonged decrease of serum calcium concentration seen in hypercalcemic, tumor-bearing nude mice. Therefore, bone resorption inhibitors like MuIFN-gamma, which ameliorate humoral hypercalcemia without an escape phenomenon, are potentially useful for the treatment of malignancy-associated hypercalcemia.

Animals↗
PubMed1992

Dopamine inhibits Na/K-ATPase in single tubules and cultured cells from distal nephron.

Dopamine decreases tubular sodium reabsorption, attributed in part to Na/K-ATPase inhibition in the proximal convoluted tubule (PCT). Because the final regulation of sodium excretion occurs in the collecting duct, where we have demonstrated specific dopamine DA1 binding sites, we examined the effects of dopamine, and of DA1 and DA2 receptor agonists on the Na/K pump in the microdissected rat cortical collecting duct (CCD) and in Madin-Darby canine kidney (MDCK) cells, a line derived from the dog distal nephron. Dopamine inhibited pump activity in CCD by approximately 40%-50%, an effect proportionally larger than in the PCT. Unlike in the latter, the effect of dopamine was reproduced by the DA1 agonist fenoldopam, which inhibited the CCD pump in dose-dependent manner (maximum, 10 microM). The DA2 agonist quinpirole was without effect, either alone or in combination with fenoldopam. These actions on Na/K-ATPase paralleled in reciprocal fashion effects on adenylate cyclase: dopamine or fenoldopam, but not quinpirole, produced a significant increase in cAMP content, and the stimulation by dopamine was blocked by SCH 23390. Inhibitors of cAMP phosphodiesterase (3-isobutyl-1-methyl-xanthine and theophylline), as well as forskolin and dibutyryl-cAMP, mimicked the effect of dopamine on the pump, underscoring the role of increased cAMP in this phenomenon. Both dopamine and fenoldopam inhibited Na/K-ATPase activity in MDCK cells. The results indicate that besides the PCT dopamine inhibits Na/K-ATPase activity in cells of the distal nephron, where its effect on the pump appears to be more pronounced and is mediated by activation of the DA1 receptor. The natriuretic effect of dopamine is probably exerted at both proximal and distal nephron sites.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Development of early bovine embryos to the blastocyst stage in serum-free conditioned medium from bovine granulosa cells.

Bovine granulosa cell-conditioned medium (BGC-CM) was prepared in a serum-free medium consisting of TCM 199, 5 micrograms/ml insulin, and 0.5 micrograms/ml aprotinin (TCM 199 IAP). Granulosa cells surrounded with embryos were denuded 24 to 30 h after in vitro fertilization. The proportion of denuded granulosa cell-free embryos that developed to the blastocyst stage in BGC-CM (43/219; 20%) as well as in the co-culture system (43/178; 24%) was significantly greater (P less than 0.001) than in fresh TCM 199 IAP medium (FM: 10/191; 5%), whereas the proportion of embryos that developed to the eight-cell stage was similar (P greater than 0.05) in all three culture systems (95/178; 53% in co-culture, 111/219; 51% in BGC-CM, and 86/191; 45% in FM, respectively). Higher rates of hatching and hatched blastocysts 8.5 days after in vitro fertilization were observed in co-culture (13/44; 29.5%) and in conditioned medium (8/39; 20.5%). On the other hand, no hatching or hatched blastocysts were obtained in the fresh medium (0/7; 0%). Cell numbers per blastocyst in BGC-CM (178.3 cells/blastocyst) were approximately two-fold higher than those in FM (97.1 cells/blastocyst). However, higher cell numbers (249.3 cells/blastocyst) were observed in co-culture with BGC than in BGC-CM. The embryotrophic activity in BGC-CM was stable upon freezing and thawing, lyophilization, and heating at 56 degrees C whereas activity was reduced by dilution in fresh medium, dialysis, pronase digestion, and heating at 80 degrees C. These results suggest that BGC cultured in a serum-free medium can synthesize and secrete an embryotrophic factor(s) that supports blastocyst formation in vitro beyond the 8- to 16-cell stage.

Animals↗
PubMed1992

Human chorionic gonadotropin causes an estrogen-mediated induction of rat ovarian carbonyl reductase.

We earlier reported that human chorionic gonadotropin (hCG) stimulates rat ovarian carbonyl reductase (CR) activity and content, and that estrogen enhances the stimulatory effect. The present study was performed to determine the mode of action of the gonadotropin. Cycloheximide (CHX) and actinomycin D (AD) were given to estradiol-pretreated immature rats 6 h before hCG treatment. The enzyme activity was measured with three substrates, and the enzyme content was determined by the method of Western-blot analysis using anti-rat ovarian CR anti-serum as the first antibody. Both protein inhibitors significantly prevented hCG from increasing the enzyme activity and content in estradiol-pretreated ovary. These results indicate that rat ovarian CR is induced by LH via the action of estrogen.

Alcohol Oxidoreductases↗
PubMed1992

Cloning of the mouse hypothalamic preprothyrotropin-releasing hormone (TRH) cDNA and tissue distribution of its mRNA.

A complementary DNA (cDNA) for mouse hypothalamic preprothyrotropin-releasing hormone (TRH) was isolated and characterized using three different combinations of the polymerase chain reaction (PCR). Using this cDNA, we examined the tissue distribution of expression of the mouse preproTRH gene and evaluated the evolutionary basis of the preproTRH gene by comparison of the cloned sequence with sequences of preproTRH in other species. The deduced protein sequence of the mouse preproTRH contained 256 amino acids featured by possessing an insertion of one amino acid as compared with that of rat preproTRH. Five repetitive copies of the TRH progenitor sequence (Lys-Arg-Gln-His-Pro-Gly-Arg/Lys-Arg) were found in the mouse preproTRH. Northern blot analysis showed an apparent single band of hypothalamic mRNA of approximately 1600 base pairs in length. The homology of the coding region of the mouse preproTRH with the rat and human preproTRH is 92 and 65% at the nucleic acid level, respectively, and 88 and 56% at the amino acid level, respectively. By means of the PCR procedure, a characteristic expression of the preproTRH mRNA was observed solely in the mouse hypothalamus and testis. Moreover, it was noteworthy to find that the degree of homology to the region containing the sixth TRH-coding sequence of the human preproTRH was higher in the mouse preproTRH than the rat counterpart.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Radiosensitizing, toxicological, and pharmacokinetic properties of hydroxamate analogues of nitroimidazoles as bifunctional radiosensitizers/chemical modifiers.

We examined the pharmacokinetics of KIH-802, potassium 2-nitroimidazole-1-acetohydroxamate, using its radioisotope-labelled compound and the acute toxicity in mice. We discovered that the concentration of KIH-802 was very low in the brain and its LD50 was nearly half the value of that of MISO. We also present here new 2-nitroimidazole radiosensitizers/chemical modifiers (KIN-804, 811, 831, 841, 844, 821, 823 and 824) designed to enhance their sensitizing ability intensely by substituting various biologically active groups, such as hydroxamic acids and oximes, with moderate lipophilicity to the aromatic ring, if necessary, through some spacers. The sensitizing effects of all compounds were estimated to be almost equal to or better than that of MISO. The results of their toxicities shows that new hydroxamates KIN-804 and 831 are less toxic than KIH-802 and MISO. Their in vitro enhancement ratios are 2.00 and 1.75, respectively, compared with those of KIH-802, MISO and SR-2508, 1.77, 1.72 and 1.72, respectively, at each dose of 1 mM for EMT6/KU single cell. We concluded that they may be superior radiosensitizers of hydroxamic acid analogues to KIH-802.

Animals↗
PubMed1992

Gastric cytoprotective anti-ulcerogenic actions of hydroxychalcones in rats.

The preventive effects of hydroxychalcone derivatives on ulcer formation induced by severe necrotizing agents such as 60% ethanol in 150 mM HCl (HCl-ethanol) and 0.2 N NaOH in rats were examined. Among the compounds tested, 2',4'-dihydroxychalcone gave the strongest activity in both experimental models and protected the gastric mucosa from the insult of either necrotizing agent at oral doses ranging from 1 to 10 mg/kg, as evidenced by a dose-related reduction in the ulcer index. The mucosal protective activity of 2',4'-dihydroxychalcone was not affected by pretreatment with indomethacin (5 mg/kg, s.c.). To investigate the detailed mechanism of the mucosal protective action of 2',4'-dihydroxychalcone, its inhibitory effects on the decrease in the hexosamine content from the gastric mucus induced by HCl-ethanol were studied by using it in combination with a dye, Alcian blue. As a result, 2',4'-dihydroxychalcone at an oral dose of 10 mg/kg inhibited the decrease in the dye-recovery from the gastric mucus induced by HCl-ethanol. PGE2 at an oral dose of 0.1 mg/kg exhibited a similar action. These results established that 2',4'-dihydroxychalcone is a potent cytoprotective agent similar to PGE2 effectively preventing gastric ulcer formation induced by strong necrotizing agents and seems to suggest that this compound protects the stomach against its own peptic secretions by reinforcement of gastric resistances. In fact, 2',4'-dihydroxychalcone prevented ulcer formation induced by water-immersion stress in rats and also showed a marked enhancement of the healing of acetic acid-induced gastric ulcers in rats.

Animals↗
PubMed1992

Analysis of the TSH receptor gene structure in various thyroid disorders: DNA from thyroid adenomas can have large insertions or deletions.

We examined the structure of the TSH receptor gene in various thyroid disorders by a restriction fragment length polymorphism (RFLP) study with a cloned human TSH receptor cDNA as a probe. Southern blot analysis of DNAs in peripheral white blood cells obtained from normal individuals revealed a single band in each of several restriction enzyme digestions, indicating that the TSH receptor gene is a single copy gene in the human genome. Although RFLPs were not detected in peripheral blood cells and thyroid tissues in patients with Graves' disease, thyroid carcinomas, or subacute thyroiditis, significant RFLPs were found in 2 of 6 patients with adenoma in all restriction enzyme digestions examined. Moreover, these RFLPs were heterozygous and adenoma specific, and these additional bands in adenoma were amplified in both cases. We conclude that there are no major abnormalities in the structure of the TSH receptor gene in patients with Graves' disease, thyroid carcinoma, or subacute thyroiditis, although there may be a possibility of point mutations, small insertions, or deletions that cannot be detected by RFLP studies, and that there are large insertions or deletions in the region, including the TSH receptor gene, in some patients with thyroid adenoma.

Blotting, Southern↗