Isami Takahashi
Biotechnology Institute
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Featured researches published by Isami Takahashi.
Biochemical and Biophysical Research Communications | 1986
Tatsuya Tamaoki; Hisayo Nomoto; Isami Takahashi; Yuzuru Kato; Makoto Morimoto; Fusao Tomita
Staurosporine, microbial alkaloid which has been known to have antifungal activity was found to inhibit markedly phospholipid/Ca++dependent protein kinase (protein kinase C) from rat brain, with an IC50 value of 2.7 nM. However, it had little effect on the binding of 3H-phorbol-12, 13-dibutyrate (PDBu) to protein kinase C. The inhibition of protein kinase C was not competitive with phospholipid. This compound also showed the strong cytotoxic effect on the growth of HeLa S3 cells, with an IC50 value of 4 X 10(-12)M under the condition of 72 hr-exposure.
Biochemical and Biophysical Research Communications | 1989
Isami Takahashi; Satoshi Nakanishi; Eiji Kobayashi; Hirofumi Nakano; Kohichi Suzuki; Tatsuya Tamaoki
Hypericin and pseudohypericin which have been isolated from plants of the Hypericum family are aromatic polycyclic diones. Daniel Meruelo et. al. have reported that hypericin and pseudohypericin showed potent antiretroviral activity including anti-human immunodeficiency virus (1,2). However, the mechanism of these antiretroviral activities has not been clarified. In the course of screening specific inhibitors of protein kinase C we have found that both compounds specifically inhibit protein kinase C with IC50 values 1.7 micrograms/ml and 15 micrograms/ml, respectively, and show antiproliferative activity against mammalian cells. These data suggest that antiretroviral activity of hypericin and pseudohypericin could be attributable to the inhibition of some phosphorylation involved by protein kinase C during viral infection of cells.
Journal of Biological Chemistry | 1997
Katsumi Shinoda; Yoshikazu Morishita; Katsutoshi Sasaki; Yuzuru Matsuda; Isami Takahashi; Tatsunari Nishi
The human α1,3-fucosyltransferase, Fuc-TVII, a key enzyme in the biosynthesis of selectin ligands, was expressed as a soluble protein-A chimeric form in a human B cell lymphoma cell line, Namalwa KJM-1, and purified using IgG-Sepharose. The enzymatic properties of recombinant soluble Fuc-TVII were then examined. Its enzyme activity was highest at pH 7.5, and the presence of 25 mm Mn2+ was required for full activity. Fuc-TVII exhibits an acceptor specificity restricted to α2,3-sialylated type 2 oligosaccharides, and the apparentK m values for α2,3-sialyl lacto-N-neotetraose and GDP-fucose were 3.08 mmand 16.4 μm, respectively. The inhibitory effects of various nucleotides on the activity of Fuc-TVII reflected its donor specificity for the nucleotide portion of GDP. Fuc-TVII was demonstrated to be useful for the synthesis of a sialyl Lewis x hexasaccharide from lacto-N-neotetraose in combination with an α2,3-sialyltransferase, ST3Gal IV. Polyethylene glycols enhanced the thermal stability of Fuc-TVII, leading to increased formation of the reaction product.
Nucleic Acids Research | 1994
Akira Asai; Satoru Nagamura; Hiromitsu Saito; Isami Takahashi; Hirofumi Nakano
Intact drugs with spirocyclopropylhexadienone moieties can be regenerated from the covalent DNA adducts induced by antitumor antibiotics duocarmycin (DUM) A, SA and some DUMA analogues in neutral aqueous solution. We detected the reversible nature of DUMs by determination of the antimicrobial activity and cytotoxicity of DUM-DNA adducts. All of the adducts selectively inhibited the growth of a sensitive strain of Bacillus but not that of the wild type strain, a property of parent DUM and its analogues. Most of the DNA adducts were also cytotoxic to HeLa S3. These results suggested that active drugs can be released from their covalent DNA adducts under these biological assay conditions. Regeneration of intact drugs was quantitatively analyzed by HPLC and the amount of free drug released from DNA adducts revealed that the rate and efficiency of this reversal were dependent on structural variables among the drugs. The differences in rates of reversibility were correlated with the biological activity of DUMs. The effect of pH, temperature and salt concentration on the regeneration of drugs from their DNA adducts suggest a catalytic role of double-helical DNA on the reversal pathway.
Glycoconjugate Journal | 1998
Katsumi Shinoda; Kenya Shitara; Yuko Yoshihara; Akira Kusano; Youichi Uosaki; So Ohta; Nobuo Hanai; Isami Takahashi
Panosialins A and B were isolated as inhibitors of an α1,3-fucosyltransferase, Fuc-TVII, which is a key enzyme in the biosynthesis of selectin ligands, from culture broth of Streptomyces sp. Panosialins A and B inhibited the Fuc-TVII activity with IC50 values of 4.8 and 5.3 μg/ml, respectively. Panosialin A suppressed expression of selectin ligands on U937 cells, and inhibited the cell adhesion to immobilized E-selectin-immunoglobulin. Panosialins are the first reported Fuc-TVII inhibitors which can suppress the biosynthesis of selectin ligands and then inhibit selectin-mediated cell adhesion.
Bioscience, Biotechnology, and Biochemistry | 2002
Hiroyuki Nagata; Hiroshi Yano; Kimihito Sasaki; Soichiro Sato; Satoshi Nakanishi; Isami Takahashi; Tatsuya Tamaoki
Lck is a Src-family tyrosine kinase that is expressed predominantly in T cells, where it plays important roles in T-cell activation. Lymphostin was isolated from Streptomyces sp. as an inhibitor of Lck. As previously reported, lymphostin inhibited Lck (IC50 0.05 μM) and the mixed lymphocyte reaction (IC50 0.009 μM). We have now examined the mechanism of inhibition by lymphostin. Lymphostin inhibited protein-tyrosine kinase activity in Jurkat T cells, demonstrating the effectiveness of the compound at the cellular level. Furthermore, lymphostin suppressed delayed-type hypersensitivity in mice. However, the inhibitory activity against Lck at the cellular level was weaker than that against the mixed lymphocyte reaction. Thus, we examined the effects of lymphostin on other kinases. Interestingly, lymphostin also inhibited phosphatidylinositol 3-kinase (IC50 0.001 μM). Consequently, we conclude that lymphostin inhibits the mixed lymphocyte reaction and delayed-type hypersensitivity not only through the blockade of Lck, but through the blockade of phosphatidylinositol 3-kinase as well.
Journal of Biological Chemistry | 1992
S Nakanishi; S Kakita; Isami Takahashi; K Kawahara; E Tsukuda; T Sano; Koji Yamada; M Yoshida; H Kase; Yuzuru Matsuda
The Journal of Antibiotics | 1987
Hirofumi Nakano; Eiji Kobayashi; Isami Takahashi; Tatsuya Tamaoki; Yasuko Kuzuu; Hideo Iba
The Journal of Antibiotics | 1987
Isami Takahashi; Eiji Kobayashi; Kozo Asano; Mayumi Yoshida; Hirofumi Nakano
The Journal of Antibiotics | 1989
Isami Takahashi; Yutaka Saitoh; Mayumi Yoshida; Hiroshi Sano; Hirofumi Nakano; Makoto Morimoto; Tatsuya Tamaoki