Details of a Researcher - Mashino, Tadahiko

Papers - Mashino, Tadahiko

Division display 81 - 100 of about 108 ／ All the affair displays >>

Inhibitory effect of a fullerene derivative, monomalonic acid C₆₀, on nitric oxide-dependent relaxation of aortic smooth muscle

Satoh Mitsutoshi, Matsuo Kazuhiro, Kiriya Hitoshi, Mashino Tadahiko, Hirobe Masaaki, Takayanagi Issei

General Pharmacology 29 ( 3 ) 345 - 351 1997.09

Research paper (scientific journal), Joint Work, ISSN 0306-3623

1. Effects of a fullerene C₆₀, derivative, monomalonic acid C₆₀ (MMA C₆₀), on endothelium-containing or denuded aorta of rabbit, trachea and ileum of guinea pig, and stomach (fundus), vas deferens and uterus of rat were studied pharmacologically. 2. MMA C₆₀ (10^-5 M) significantly reduced the maximum response of the relaxation induced by acetylcholine in endothelium containing thoracic aorta of rabbit, and the acetylcholine induced relaxation was recovered in the presence of superoxide dismutase (SOD, 250 units/ml). 3. Nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused the relaxation of aorta without endothelium in a concentration dependent manner, and the concentration-response curve was shifted to the right in the presence of MMA C₆₀. This inhibitory effect of the derivative was also masked in the presence of superoxide dismutase (SOD). 4. Sodium nitroprusside-induced relaxation was not affected by either MMA C₆₀ Or SOD. In the other tissues, this C₆₀ derivative had no effect on the responses induced by any agonist. 5. These observations indicate that MMA C₆₀ inhibits the endothelium dependent relaxation induced by acetylcholine but does not affect the agonist-induced contractile response of smooth muscle.

Access to Document (DOI)

Inhibitory effects of a fullerene derivative, dimalonic acid C60, on nitric oxide-induced relaxation of rabbit aorta.

Satoh M., Matsuo K., Kiriya H., Mashino T., Nagano T., Hirobe M., Takayanagi I.

European Journal of Pharmacology 327 ( 2-3 ) 175 - 181 1997.05

Research paper (scientific journal), Joint Work, ISSN 0014-2999

Dimalonic acid C60 (10(-5) M), a new fullerene derivative, produced an augmentation of phenylephrine-induced tone and reduced both the acetylcholine-induced maximum relaxation and the amplitude of substance P (10(-8) M)-induced relaxation in endothelium-containing thoracic aorta of rabbit; the acetylcholine- and substance P-induced relaxation was restored in the presence of superoxide dismutase (250 U/ml). Dimalonic acid C60 (10(-5) M) did not influence the phenylephrine-induced contractile response in the absence of endothelium, but the acetylcholine-induced relaxation was eliminated by removal of the endothelium. Superoxide anion generation, using hypoxanthine (1 mM)/xanthine oxidase (16 mU/ml), reduced the acetylcholine-induced relaxation and produced an augmentation of phenylephrine-induced tone in endothelium-containing strips; these effects were negated by the addition of superoxide dismutase (250 U/ml). A nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of dimalonic acid C60. This inhibitory effect of dimalonic acid C60 was also masked in the presence of superoxide dismutase. Sodium nitroprusside-induced relaxation was not affected by either dimalonic acid C60 or superoxide dismutase. These observations suggest that dimalonic acid C60 inhibits endothelium (nitric oxide)-dependent agonist-induced relaxation through the production of superoxide.

Substituent elimination from p-substituted phenols by cytochrome P450 ipso-substitution by the oxygen atom of the active species

Ohe Tomoyuki, Mashino Tadahiko, Hirobe Masaaki

Drug Metabolism and Disposition 25 ( 1 ) 116 - 122 1997.01

Research paper (scientific journal), Joint Work, ISSN 0090-9556

When various p-substituted phenols (substituent = NO₂, CN, CH₂OH, COCH₃, COPh, COOH, F, Cl, and Br) were incubated with rat liver microsomes, the substituent was eliminated to produce hydroquinone, and the reaction was inhibited by CO and a cytochrome P450-specific inhibitor. In the case of p- cresol (substituent = CH₃), p-toluquinol was formed instead of hydroquinone. Experiments using ¹⁸O₂ proved that the elimination is accompanied with ipso-substitution by the oxygen atom of the active species in cytochrome P450. These results are similar to those in a cytochrome P450 chemical model system (Ohe, T., et al., Tetrahedron Lett. 42, 7681-7684, 1995), implying that the model is a good mimic of cytochrome P450. Substrates that lack a hydroxy group, namely p-substituted toluenes, did not undergo the reaction, thus indicating that a hydroxy group at the p-position to the eliminated substituent is necessary for this pathway. This is the same as the result obtained with the cytochrome P450 model. Finally, to elucidate how the substituent is eliminated, we attempted to detect the product derived from the eliminated group with several substrates. Results indicated that the mechanism of the substituent elimination can be divided into two types: the substituent is eliminated as an anion or as a cation.

Singlet oxygen production from fullerene derivatives

Hamano Takeshi, Okuda Kensuke, Mashino Tadahiko, Hirobe Masaaki, Arakane Kumi, Ryu Akemi, Mashiko Shinrou, Nagano Tetsuo

Chemical Communications ( 1 ) 21 - 22 1997

Research paper (scientific journal), Joint Work, ISSN 1359-7345

Superoxide radical quenching and cytochrome C peroxidase-like activity of C₆₀-dimalonic acid, C₆₂(COOH)₄

Okuda Kensuke, Mashino Tadahiko, Hirobe Masaaki

Bioorganic and Medicinal Chemistry Letters 6 ( 5 ) 539 - 542 1996.03

Research paper (scientific journal), Joint Work, ISSN 0960-894X

Access to Document (DOI)

Novel oxidative pathway of para-substituted phenols in cytochrome P450 chemical model

Ohe Tomoyuki, Mashino Tadahiko, Hirobe Masaaki

Tetrahedron Letters 36 ( 42 ) 7681 - 7684 1995.10

Research paper (scientific journal), Joint Work, ISSN 0040-4039

Access to Document (DOI)

Hydroxylation of benzene by horseradish peroxidase and immobilized horseradish peroxidase in an organic solvent

Akasaka Reiko, Mashino Tadahiko, Hirobe Masaaki

Bioorganic and Medicinal Chemistry Letters 5 ( 16 ) 1861 - 1864 1995.08

Research paper (scientific journal), Joint Work, ISSN 0960-894X

Horseradish peroxidase (HRP) catalyzed hydroxylation of benzene with an oxidant when benzene was used as the reaction solvent. HRP immobilized on poly(γ-methyl-L-glutamate) also catalyzed the reaction with higher activity than that of free HRP. The results of the reaction using [¹⁸O]hydrogen peroxide show that free and immobilized HRP incorporated the oxygen atom of the reactive species into the product, indicating that both forms of HRP can catalyze hydroxylation of benzene in an analogous manner to that of cytochrome P450. © 1995.

Access to Document (DOI)

Oxidation of [60]fullerene by cytochrome P450 chemical models

Hamano Takeshi, Mashino Tadahiko, Hirobe Masaaki

Journal of the Chemical Society, Chemical Communications ( 15 ) 1537 - 1538 1995

Research paper (scientific journal), Joint Work, ISSN 0022-4936

Access to Document (DOI)

Novel Metabolic Pathway of Arylethers by Cytochrome P450

Ohe T., Mashino T., Hirobe M.

Archives of Biochemistry and Biophysics 310 ( 2 ) 402 - 409 1994.05

Research paper (scientific journal), Joint Work, ISSN 0003-9861

We have found a novel metabolic pathway of arylethers, involving the cleavage of the oxygen-aromatic ring bond. When p-(p-nitrophenoxy)phenol was utilized as a substrate, cleaved products, p-nitrophenol and p-benzoquinone, were formed in two cytochrome P450 model systems, meso-tetraphenylporphinatoiron(III) chloride-NaBH₄/O₂ system and meso-tetrakis (2,6-difluorophenyl)porphinatoiron(III) chloride-m-chloroperoxybenzoic acid (mCPBA) system. Rat liver microsomes also catalyzed this reaction, which was inhibited by a cytochrome P450-specific inhibitor, and it was confirmed that this cleavage proceeded in vivo. Further, experiments using [¹⁸O]mCPBA and ¹⁸O₂ proved that the cleavage reaction is accompanied with the ipso-substitution by the oxygen atom of the active species in both cytochrome P450 model system and cytochrome P450. When the microsomal reactions of p-(p-nitrophenoxy)phenol analogues which lack a hydroxy group, namely p-nitrophenoxybenzene, p-(p-nitrophenoxy) anisole, and p-(p-nitrophenoxy) toluene, were investigated, the cleavage reaction occurred via p-(p-nitrophenoxy)phenol in the cases of p-nitrophenoxybenzene and p-(p-nitrophenoxy)anisole, indicating that a hydroxy group at the p-position to the ether bond is necessary for this pathway. This metabolic pathway appears to be important, because a diarylether linkage, which is very stable and has generally been thought to resist metabolism, is cleaved and benzoquinone, a highly toxic metabolite, is formed. © 1994 Academic Press. All rights reserved.

Access to Document (DOI)

Hydroxylation of benzene by immobilized cytochrome c in an organic solvent

Akasaka Reiko, Mashino Tadahiko, Hirobe Masaaki

Journal of the Chemical Society, Perkin Transactions 1 ( 13 ) 1817 - 1821 1994

Research paper (scientific journal), Joint Work, ISSN 1472-7781

Recently we showed that cytochrome c (cyt.c) has some cytochrome P450 (P450)-like substrate oxidation activity, which was enhanced by immobilization on poly-γ-methyl-L-glutamate. We now report that immobilized cyt.c catalysed hydroxylation of benzene when benzene containing a small amount of water was used as the reaction solvent, whereas free cyt.c did not catalyse the reaction. The EPR spectrum of immobilized cyt.c showed that the immobilization had caused a change in the protein conformation, and this might have led cyt.c to acquire the new activity. The results of the reaction using [ ¹⁸O]m-chloroperbenzoic acid (mCPBA) or [¹⁸O] molecular dioxygen showed that 59% of the oxygen atom of the product, phenol, was derived from the oxidant, and 33% from molecular dioxygen. When [18O]mCPBA was used as an oxidant, the value of deuterium isotope effect (k_H/k _D)was 1.08 when ¹⁸O was incorporated into the product, and 1.48 when ¹⁸O was not incorporated. These results indicate that immobilized cyt.c catalysed hydroxylation of benzene via two major pathways, of which one resembles that of P450.

Application of Chemical Cytochrome P450 Model Systems to Studies on Drug Metabolism .VI

Doi T., Mori T., Mashino T., Hirobe M.

Biochemical and Biophysical Research Communications 191 ( 2 ) 737 - 743 1993.03

Research paper (scientific journal), Joint Work, ISSN 0006-291X

Polypeptide-bound porphyrinatoiron(III) effectively catalyzed the N,N coupling reaction of N-methylaniline in the presence of NaBH₄/O₂/tetramethyl-ammonium hydroxide or cumenehydroperoxide, whereas the corresponding non-bound monomer porphyrinatoiron(III) had little catalytic activity. Rat liver microsomes also catalyzed the N,N-coupling which was inhibited by cytochrome P-450 specific inhibitors, SKF-525A and metyrapone. The polypeptide-bound porphinatoiron(III) appears to be an excellent cytochrome P450 model for drug metabolism studies. © 1993 Academic Press. All rights reserved.

Access to Document (DOI)

Cytochrome P450-like Substrate Oxidation Catalyzed by Cytochrome c and Immobilized Cytochrome c

Akasaka R., Mashino T., Hirobe M.

Archives of Biochemistry and Biophysics 301 ( 2 ) 355 - 360 1993.03

Research paper (scientific journal), Joint Work, ISSN 0003-9861

Cytochrome c (cyt.c) was shown to catalyze cytochrome P450 (P450)-like oxidative reactions, such as N-, and 0-demethylation, S-oxidation, and epoxidation of olefins. A more detailed examination showed that (i) N-methylcarbazole and thioanisole oxidation with H₂¹⁸O₂ catalyzed by cyt.c resulted in introduction of ¹⁸O into the product, and (ii) during the epoxidation of cis-stilbene catalyzed by cyt.c, the stereochemistry of the substrate was retained and ¹⁸O was introduced when H₂¹⁸O₂ was used as an oxidant. These results show that cyt.c catalyzed N-demethylation, S-oxidation, and epoxidation in the same manner as P450. To utilize these P450-like reactivities effectively, cyt.c was immobilized on poly-γ-methyl-L-glutamate. Up to 99% of the cyt.c used was immobilized. This immobilized cyt.c catalyzed N-demethylation, S-oxidation, and epoxidation in the same manner as both P450 and free cyt.c, and the activities of these reactions were increased by the immobilization. In N-demethylation of N,N-dimethylaniline with cumene hydroperoxide (CHP) catalyzed by cyt.c, the V_max for CHP was increased by 4.4-fold by the immobilization of the enzyme, while the K_m remained unchanged. Since P450 is involved in the metabolism of many xenobiotics, the above results suggest that immobilized cyt.c may be useful in drug metabolism research. © 1993 Academic Press. All rights reserved.

Access to Document (DOI)

Oxygen activation by iron(III)-porphyrin/NaBH₄/Me₄N·OH system as cytochrome P-450 model. Oxygenation of olefin, N-dealkylation of tertiary amine, oxidation of sulfide, and oxidative cleavage of ether bond

Mori T., Santa T., Higuchi T., Mashino T., Hirobe M.

Chemical and Pharmaceutical Bulletin 41 ( 2 ) 292 - 295 1993

Research paper (scientific journal), Joint Work, ISSN 0009-2363

Oxygenation of olefin, N-dealkylation of tertiary amine, oxidation of sulfide, and oxidative cleavage of ether bond were conducted with tetraphenylporphyrinatoiron(III) (Fe³⁺TPPCl), NaBH₄, Me₄N·OH, and molecular dioxygen in benzene-methanol solution. Fe³⁺TPPCl, NaBH₄, and molecular dioxygen were essential for these reactions and the yields were decreased when Me₄N·OH was absent. Olefins were converted to alcohols, which were not produced from the corresponding epoxides under the same conditions. In styrene oxygenation, an electron-donating substituent on the substrate decreased the reactivity, whereas in N,N-dimethylaniline demethylation, it enhanced the reactivity. Despite the use of the same reagents, the key intermediates of these two reactions are different. Fe²⁺TPP-σ-alkyl complexes produced from Fe³⁺TPPCl, olefin, and NaBH₄ were identified as intermediates under anaerobic conditions. Fe²⁺TPP-σ-alkyl complex reacted with molecular dioxygen to give oxygenated products. Examination of the relative reactivities of p-substituted N,N-dimethylanilines in the NaBH₄ reaction system revealed first, that the demethylation proceeded via one-electron abstraction, and second, that the reactive species of the demethylation reactions seems to be an iron-oxenoid.

¹⁸O incorporation from H₂ ¹⁸O₂ in the oxidation of N-methylcarbazole and sulfides catalyzed by microperoxidase-11

Nakamura Shigeo, Mashino Tadahiko, Hirobe Masaaki

Tetrahedron Letters 33 ( 37 ) 5409 - 5412 1992.09

Research paper (scientific journal), Joint Work, ISSN 0040-4039

Microperoxidase-11 (MP-11), prepared by pepsin digestion of cytochrome c, contains protoheme IX and one proximal histidine ligand. MP-11 oxygenated N-methylcarbazole, methyl phenyl sulfide, and phenacyl phenyl sulfide with 80%, 100%, and 96% ¹⁸O atom incorporation from H₂
¹⁸O₂, respectively. These results indicate that the oxygen atom on heme iron of MP-11 immediately rebinds to one-electron-oxidized intermediates of the substrates and that MP-11 catalyzes N-demethylation through a cytochrome P-450-like mechanism rather than a peroxidase-like mechanism. © 1992.

Access to Document (DOI)

Substrate oxidation catalyzed by heme-undecapeptide, microperoxidase-11 in the presence of iodosylbenzene and cumene hydroperoxide

Nakamura S., Mashino T., Hirobe M.

Journal of Pharmacobio-Dynamics 14 ( 11 ) 1991

Research paper (scientific journal), Joint Work, ISSN 0386-846X

Metabolism and penetration through blood-brain barrier of parkinsonism-related compounds. 1,2,3,4-Tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline

Kikuchi K., Nagatsu Y., Makino Y., Mashino T., Ohta S., Hirobe M.

Drug Metabolism and Disposition 19 ( 1 ) 257 - 262 1991

Research paper (scientific journal), Joint Work, ISSN 0090-9556

¹⁴C-Labeled 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were synthesized, and their metabolism and tissue distribution were studied. Both compounds showed similar metabolic patterns. In 24 hr after po administration (50 mg/kg) to rats, 76% of TIQ and 72% of 1MeTIQ were excreted unchanged, and 2.7 and 8.7% were excreted as the 4-hydroxyl derivatives, 4-hydroxy-TIQ and 4-hydroxy-1MeTIQ, respectively. Small amounts of N-methylated metabolites, 2-methyl-TIQ (0.4%) and 2-methyl-1MeTIQ (0.7%) were detected. Isoquinoline (2.5%) also was found as a metabolite of TIQ and 1-methyl-3,4-dihydroisoquinoline (1.0%) was found as a metabolite of 1MeTIQ. The concentration of labeled compounds in the brain was about 4.5-fold higher than the blood concentration at 4 hr after dosing, and over 90% was unchanged TIQ or 1MeTIQ. These data indicate that TIQ and 1MeTIQ easily passed through the blood-brain barrier and were concentrated in the brain. Thus, it appears that TIQ and 1MeTIQ as endogenous or exogenous amines may accumulate in the brain and may be related to the onset of Parkinson's disease.

Sulfide oxidation, amine N-demethylation, and olefin oxidation by heme-undecapeptide, microperoxidase-11, in the presence of hydrogen peroxide

Mashino Tadahiko, Nakamura Shigeo, Hirobe Masaaki

Tetrahedron Letters 31 ( 22 ) 3163 - 3166 1990

Research paper (scientific journal), Joint Work, ISSN 0040-4039

Access to Document (DOI)

Metabolism and blood-brain barrier permeability of tiqs

Ohta S., Tachikawa O., Makino Y., Kikuchi K., Mashino T., Hirobe M.

Journal of Pharmacobio-Dynamics 12 ( 3 ) 1989

Research paper (scientific journal), Joint Work, ISSN 0386-846X

The reactivity of superoxide

Yamamoto Hiroshi, Mashino Tadahiko, Nagano Tetsuo, Hirobe Masaaki

Tetrahedron Letters 30 ( 31 ) 4133 - 4136 1989

Research paper (scientific journal), Joint Work, ISSN 0040-4039

Access to Document (DOI)

Reactions of hypochlorite with catalase

Mashino Tadahiko, Fridovich Irwin

Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular 956 ( 1 ) 63 - 69 1988.08

Research paper (scientific journal), Joint Work, ISSN 0167-4838

OCl^-/HOCl imposed a rapid inactivation of catalase (hydrogen-peroxide: hydrogen-peroxide oxidoreductase, EC 1.11.1.6), some of which was slowly reversible upon subsequent exposure to H₂O₂. Ethanol accelerated this restoration of activity by H₂O₂. OCl^- caused biphasic changes in the visible absorption spectrum of catalase, which were partially reversed by dithionite. A scheme of reactions involving axial ligation of one or two OCl^- to heme iron, followed by heterolytic or homolytic cleavages of the OCl bond, is proposed to account for the behavior of the system. © 1988.

Access to Document (DOI)

　 Previous page - Next page 　