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M Mutoh

Publications and source records attributed to M Mutoh.

29 records · Page 2Linked to original sources
PubMed1997

Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin.

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.

Amino Acid Sequence↗
PubMed1994

Adenosine triphosphate-dependent transport of leukotriene C4 by membrane vesicles prepared from cisplatin-resistant human epidermoid carcinoma tumor cells.

BACKGROUND: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-conjugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. PURPOSE: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). METHODS: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37 degrees C. RESULTS: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-dependent. In contrast, the ATP-dependent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or verapamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(beta,gamma-methylene) triphosphate, was not effective. CONCLUSIONS: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. IMPLICATIONS: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells.

Adenosine Triphosphate↗
PubMed1994

Active efflux system for cisplatin in cisplatin-resistant human KB cells.

Mutants, KCP-4 and PC-5, resistant to an anticancer agent, cisplatin, were selected in multiple steps from human epidermoid KB carcinoma cells and human prostate PC-3 carcinoma cells, respectively. KCP-4 and PC-5 were 63 and 10 fold more resistant to cisplatin than the parental cells, respectively. KCP-4 cells exhibited increased resistance to cisplatin analogues and were also slightly cross-resistant to melphalan, cyclophosphamide, mitomycin C and methotrexate. KCP-4 cells were not cross-resistant to doxorubicin, daunorubicin, vincristine or CdSO4. The accumulations of cisplatin in KCP-4 cells and PC-5 in medium containing 50 microM cisplatin were approximately 20% of those in the parental cells. Revertant analysis suggested that a defect in cisplatin accumulation may be related to cisplatin resistance in PC-5 cells. The uncoupling agent of oxidative phosphorylation, 2,4-dinitrophenol, increased the accumulation of cisplatin in KCP-4 and cisplatin-resistant human prostate carcinoma PC-5 cells to nearly the same level as in their parental KB-3-1 and human prostate carcinoma PC-3 cells without 2,4-dinitrophenol, but did not increase accumulation in KB-3-1 and PC-3 cells. Addition of glucose in the medium inhibited the enhancement of cisplatin accumulation in KCP-4 cells by 2,4-dinitrophenol. Enhanced active efflux of cisplatin from KCP-4 cells was observed. A cell-cell hybridization test showed that the cisplatin resistance and the accumulation defect behaved as codominant traits. These data suggest that an active efflux system for cisplatin exists in cisplatin-resistant KCP-4 cells.

Biological Transport, Active↗
PubMed1994

Panclicins, novel pancreatic lipase inhibitors. I. Taxonomy, fermentation, isolation and biological activity.

Panclicins A, B, C, D, and E are novel pancreatic lipase inhibitors isolated from Streptomyces sp. NR 0619. Structurally, panclicins A, B, C, D, and E are analogues of tetrahydrolipstatin (THL), which contains a beta-lactone and a N-formyl leucine ester, and the IC50s of panclicins A, B, C, D, and E for porcine pancreatic lipase are 2.9, 2.6, 0.62, 0.66, and 0.89 microM, respectively. The potency of the inhibitory activity of each compound is attributed to the amino acid moiety of each structure. The panclicins are either glycine-type compounds such as panclicins C, D, E, which are two to threefold more potent than THL, or they are alanine-type compounds such as panclicins A and B, which are less potent than the glycine compounds. The inhibitory profiles of the panclicins for other lipases such as post-heparin plasma lipases and bacterial lipases are similar to those for pancreatic lipase. Panclicins A, B, C, D, and E, in a manner similar to THL, irreversibly inhibit pancreatic lipase. However, the compounds don't irreversibly inhibit the enzyme as strongly as THL does.

Animals↗
PubMed1994

Panclicins, novel pancreatic lipase inhibitors. II. Structural elucidation.

Panclicins A-E are novel and potent pancreatic lipase inhibitors produced by Streptomyces sp. NR 0619. Their structures have been elucidated based on NMR and FAB-MS experiments. The relative configurations have also been determined by NMR experiments. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates of panclicins A and B and by modified Mosher's method on a derivative of panclicin A. They are structurally related to beta-lactone esterase inhibitors of microbial origin, lipstatin, valilactone, ebelactones and esterastin. Panclicins also contain a beta-lactone structure with two alkyl chains, one of which has an N-formylalanyloxy or N-formylglycyloxy substituent.

Lactones↗
PubMed1993

Involvement of free radicals in cisplatin-induced emesis in Suncus murinus.

The participation of free radicals in cisplatin-induced emesis was investigated in the house musk shrew, Suncus murinus. Thiobarbituric acid (TBA) values, which indicate the degree of lipid peroxidation, in brain, liver and small intestine were increased significantly 60 min after the treatment with cisplatin (20 mg/kg, i.p.). Moreover, cisplatin (20 mg/kg, i.p.)-induced emesis was prevented by intraperitoneal injection of N-(2-mercaptopropionyl)glycine (MPG), a radical scavenging agent, with ID50 value of 130 mg/kg. However, MPG did not block the emesis induced by copper sulfate (40 mg/kg, p.o.), veratrine (0.5 mg/kg, s.c.) or serotonin (10 mg/kg, i.p.). We also investigated the effects of superoxide dismutase conjugated to polyethylene glycol and catalase, but the number of vomiting episodes and latency did not change significantly when these agents were intraperitoneally injected 30 min prior to or 20 min after the administration of cisplatin. MPG did not affect the antitumor effect of cisplatin tested in vitro. These results suggest that free radicals mediate emesis caused by cisplatin and that radical scavengers may become a new class of prophylactic drug against cancer-chemotherapeutic drug-induced emesis.

Animals↗
PubMed1993

Synthesis, structure and antitumor activity of a new water-soluble platinum complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato(2-)-O2] platinum(II).

The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with 2,4-dioxopentanoic acid gave a water-soluble complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato (2-)-O2] platinum(II). The structure of the complex was determined by X-ray crystal analysis. The data indicated a chelation of the acetylacetonato part of 2,4-dioxo-pentanoic acid to platinum(II). The complex showed moderate antitumor activity against murine leukemia L1210 in mice (T/C = 195% at a dose of 200 mg/kg) and high activity against cisplatin-resistant L1210 leukemia (T/C = 275% at a dose of 25 mg/kg).

Animals↗
PubMed1992

Synthesis, structure and antitumor activity of a water-soluble platinum complex, (1R,3R,4R,5R)-(-)-quinato(1R,2R-cyclohexanediamine)platinum (II).

The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with (-)-quinic acid gave a water soluble complex, (-)-quinato(1R,2R-cyclohexanediamine)platinum(II). The crystal structure of the complex was determined by X-ray analysis. The data indicate a chelation of the alpha-hydroxycarboxylic acid part of quinic acid to platinum(II). The complex shows moderate antitumor activity against murine leukemia L1210 at high doses (T/C x 100 = 179% at a dose of 200 mg/kg).

Animals↗
PubMed1992

Cisplatin-induced emesis in Suncus murinus.

Emetic responses to cisplatin and participation of vagal innervation in emesis were studied in suncus. Intraperitoneal and intravenous administration of cisplatin caused dose-dependent emesis. ED50 values, latencies and frequencies were not significantly different between the two administrations. Cis-diaqodiammineplatinum (DAP), an active metabolite of cisplatin, also induced emesis, but with significantly shorter latency. Vagotomy completely abolished both types of vomiting. These results suggest that cisplatin is metabolized to DAP that subsequently causes emesis through stimulation of the vagus afferent.

Animals↗
PubMed1986

HLA in Buerger's disease.

Recent studies have focused on the possible genetic factor(s) in the pathogenesis of Buerger's disease as well as in Takayasu's disease. We investigated HLA-A, B, C, DR, and DQ antigens in 59 patients with Buerger's disease to confirm statistically significant high frequencies of Aw24, Bw40, Bw54, Cw1, and DR2 antigens and a low frequency of DR9 and DRw52 as compared with those in 152 normal Japanese individuals. As the haplotpye Aw24-Bw54-Cw1-DR4 is known to be common among Japanese, a significantly high frequency of haplotype Bw54-DR2 found in cases of Buerger's disease, instead of that of Bw54-DR4, may suggest a possible cross-linkage occurrence in chromosome 6, which could prove to be an important causative phenomenon in the pathophysiology of Buerger's disease.

Disease Susceptibility↗