Curriculum Vitaes
Profile Information
- Affiliation
- Adviser of School of Medicine (Professor Emeritus(Fujita Health University, Nagoya University, Tokyo Insititute of Technology)), School of Medicine, Fujita Health University
- Degree
- (BLANK)
- J-GLOBAL ID
- 200901072288633974
- researchmap Member ID
- 1000102740
Research Interests
2Research Areas
1Education
4Committee Memberships
5Awards
9Papers
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NEUROCHEMISTRY INTERNATIONAL, 9(2) 281-286, 1986 Peer-reviewed
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NEUROCHEMISTRY INTERNATIONAL, 8(3) 413-416, 1986 Peer-reviewed
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NEUROCHEMISTRY INTERNATIONAL, 8(3) 423-428, 1986 Peer-reviewed
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 134(2) 749-754, Jan, 1986 Peer-reviewed
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BRAIN RESEARCH, 361(1-2) 77-90, Dec, 1985 Peer-reviewed
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Neuroscience Letters, 57 301-305, Jun, 1985 Peer-reviewedPargyline, an inhibitor of monoamine oxidase (MAO), prevented 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inhibition of dihydroxyphenylalanine (DOPA) production by tyrosine hydroxylase (TH) system in rat striatal tissue slices. The result suggests that the metabolism of MPTP in rat striatal tissue slices by MAO is necessary for the expression of the inhibitory effect. 1-Methyl-4-phenylpyridinium ion (MPP+), the metabolic product of MPTP by MAO, also inhibited DOPA formation in rat striatal tissue slices. The concentration of MPP+ producing significant inhibition was lower than that of MPTP, and the maximal inhibition produced by MPP+ was greater than that caused by MPTP. Since MPP+ at a concentration of 10-4 M had no effect on the activity of pure TH in vitro, the inhibition of DOPA formation in tissue slices induced by MPP+ may not be due to direct inhibition of TH. Although hydroxylated derivatives of MPTP were reported to inhibit dihydropteridine reductase in vitro at lower concentrations than MPTP, 1-methyl-4-(p-hydroxyphenyl)-1,2,3,6-tetrahydropyridine showed only weak inhibition for tyrosine hydroxylation in striatal tissue slices. © 1985.
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Brain Research, 337 193-196, Jun, 1985 Peer-reviewed1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a nigrostriatal neurotoxin in humans and primates, at 10-5 M inhibited hydroxylation of tyrosine to 3,4-dihydrophenylalanine (DOPA), the rate-limiting step of dopamine synthesis, in tissue slices of the striatum and nucleus accumbens of the rat. Nomifensine, an inhibitor of dopamine uptake, reversed the inhibition but sulpiride, a dopamine receptor antagonist, did not affect the inhibition. MPTP at 10-5 M inhibited neither the purified tyrosine hydroxylase nor dihydropteridine reductase in vitro. The level of total biopterin did not change significantly, but the tetrahydrobiopterin level was decreased in the striatal slices incubated in the presence of MPTP. These results suggest that MPTP inhibits dopamine synthesis in situ at the tyrosine hydroxylase step probably through inhibition of dihydropteridine reductase. © 1985.
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NEUROCHEMISTRY INTERNATIONAL, 7(5) 761-763, 1985 Peer-reviewed
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BIOGENIC AMINES, 2(2) 125-129, 1985 Peer-reviewed
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JOURNAL OF NEURAL TRANSMISSION, 62(3-4) 321-329, 1985 Peer-reviewed
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JOURNAL OF NEUROCHEMISTRY, 44(3) 755-758, 1985 Peer-reviewed
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CLINICA CHIMICA ACTA, 152(3) 307-314, 1985 Peer-reviewed
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JOURNAL OF NEURAL TRANSMISSION, 62(1-2) 107-115, 1985 Peer-reviewed
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ANALYTICAL BIOCHEMISTRY, 147(1) 80-85, 1985 Peer-reviewed
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LIFE SCIENCES, 37(17) 1605-1611, 1985 Peer-reviewed
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JOURNAL OF CHROMATOGRAPHY, 344(NOV) 93-100, 1985 Peer-reviewed
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 133(1) 202-207, 1985 Peer-reviewed
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ANALYTICAL BIOCHEMISTRY, 150(2) 408-414, 1985 Peer-reviewed
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BIOCHEMICAL MEDICINE, 34(1) 52-59, 1985 Peer-reviewed
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BIOCHEMICAL PHARMACOLOGY, 34(15) 2637-2643, 1985 Peer-reviewed
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JOURNAL OF CHROMATOGRAPHY, 341(1) 23-30, 1985 Peer-reviewed
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Brain Research, 299 380-382, May, 1984 Peer-reviewedTyrosine hydroxylase activity was measured in the caudate nucleus and substantia nigra (pars compacta) of sinoaortic-denervated (SAD) and sham-operated (SO) rats 3 days after operation. The SAD groups had approximately a 50%, statistically significant, reduction of enzyme activity in both regions and also a significant reduction of dopamine in caudate nucleus. These results suggest a probable link between cortico-somatomotor integration and neural input from arterial baroreceptor neural pathways. © 1984.
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Japanese Journal of Clinical Chemistry, 13(5) 299-302, 1984 Peer-reviewedThe distribution of three peptidases that may cleave collagen-derived peptides, PZ-peptidase (PZ-Pro-Leu-Gly-Pro-D-Arg as substrate), SU-peptidase (Succinyl-Gly-Pro-Leu -Gly-Pro-4-methylcoumarinamide assub strate), and dipeptidyl-aminopeptidase IV (DAP-IV, Gly-Pro-p-nitroanilide as substrate), were measured in human tissues. The activity of PZ-peptidase was about 1/20 of that of SU-peptidase, but the activities of two enzymes were similarly distributed various tissues, whereas the activity of DAP-IV was predominant in kidney and submandibular gland and relatively high in the digestive system such as pancreas, liver, and small intestine. The activity of PZ-peptidase and that of SU-peptidase had weak correlation, but the activity of DAP-IV had no correlation with that of PZ-peptidase or SU-peptidase. The results indicate that PZ-peptidase and SU-peptidase may be similar enzymes and that DAP-IV may have different functions from those of PZ-peptidase and SU-peptidase. Since the correlation between PZ-peptidase and SU-peptidase was weak, clinical data obtained by SU-peptide should not be assumed to be identical with those obtained by PZ-peptide. © 1984, Japan Society of Clinical Chemistry. All rights reserved.
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CLINICA CHIMICA ACTA, 138(3) 275-282, 1984 Peer-reviewed
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ANALYTICAL BIOCHEMISTRY, 141(2) 472-480, 1984 Peer-reviewed
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NEUROCHEMISTRY INTERNATIONAL, 6(4) 475-480, 1984 Peer-reviewed
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JOURNAL OF CHROMATOGRAPHY, 308(JUN) 43-53, 1984 Peer-reviewed
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BIOCHIMICA ET BIOPHYSICA ACTA, 789(2) 111-118, 1984 Peer-reviewed
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BIOGENIC AMINES, 1(2) 171-178, 1984 Peer-reviewed
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BIOGENIC AMINES, 1(1) 51-62, 1984 Peer-reviewed
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MOLECULAR AND CELLULAR BIOCHEMISTRY, 63(1) 53-58, 1984 Peer-reviewed
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BIOCHEMICAL MEDICINE, 31(2) 140-146, 1984 Peer-reviewed
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ANALYTICAL BIOCHEMISTRY, 138(1) 125-132, 1984 Peer-reviewed
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GANN, 75(12) 1089-1099, 1984 Peer-reviewed
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BIOGENIC AMINES, 1(3) 259-266, 1984 Peer-reviewed
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BIOMEDICAL RESEARCH-TOKYO, 5(1) 77-82, 1984 Peer-reviewed
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Advances in neurology, 40 467-473, 1984In parkinsonian brain, TH and the BP cofactor, as well as DBH and PNMT with phenylethanolamine as substrate, are decreased. However, decrease in AADC with L-DOPA as substrate was not statistically significant. TH activity has also been shown to be decreased in striatonigral degeneration and Shy-Drager syndrome. TH reduction only in striatum but not in substantia nigra was found in a case of juvenile Parkinson's disease. Changes in AADC with L-DOPA or L-5-HTP as substrates varied in parkinsonian brains. PNMT with norepinephrine as substrate was also significantly decreased in parkinsonian brains. After administration of tyrosine to mice, the BP concentration was increased in striatum, adrenals, and serum. Mean BP concentration in serum of parkinsonian patients was slightly but significantly lower than that in controls. The serum BP increased three- to sevenfold in response to an oral tyrosine load in controls, whereas there was no increase or only a minor one (less than threefold) in parkinsonian patients. Our present results indicate that all catecholamine-synthesizing enzymes and BP synthesis may be impaired in Parkinson's disease.
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Neurochem. Int., 6(4) 509-512, 1984 Peer-reviewedBy use of in vivo voltammetry technique, in vivo release of dopamine and serotonin in the striatum under stress was found to be more prominent in spontaneously hypertensive rats (SHR) at 4 weeks of age than in control Wistar-Kyoto rats (WKY). Simultaneously, a greater activation of tyrosine hydroxylase in the striatum was demonstrated in SHR than in WKY. These results indicate that SHR is more susceptible to stress in the central monoaminergic neurons than WKY. © 1984.
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Jpn. Heart J., 25 820-822, Jan 1, 1984 Peer-reviewedThe abnormality in catecholamine metabolism in the brain of SHR has been examined by use of in vivo voltammetry technique. In vivo release of dopamine and serotonin in the striatum under acute stress was more prominent in SHR at 4 weeks of age than in normotensive Wistar-Kyoto rats (WKY). Acute activation after stress of in vitro tyrosine hydroxylase activity was observed only in SHR, but tryptophan hydroxylase activity did not change significantly. It is concluded that central monoaminergic neurons are more susceptible to stress in SHR than those in WKY. © 1984, International Heart Journal Association. All rights reserved.
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Japanese Journal of Clinical Chemistry, 12(1) 89-93, 1983 Peer-reviewedMultiple forms of glycylprolyl dipeptidyl-aminopeptidase (GP-DAP) were analyzed in human serum, liver, kidney, spleen, and lymphocytes by our methods based on electrophoresis with fluorometry using 7-glycyl-proline-4-methylcoumarinamide tosylate as substrate. Four peaks of the activity of GP-DAP were separated by the electrophoretic analysis. The main peak (peak III) in normal human serum was found to coincide with that in the human spleen and lymphocytes. Peak II and peak IV enzymes, which were predominantly observed in human sera from patients with hepatitis, coincided with the main peaks of crude and pure enzymes in the liver and kidney, respectively. © 1983, Japan Society of Clinical Chemistry. All rights reserved.
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BIOCHEMISTRY INTERNATIONAL, 7(3) 387-393, 1983 Peer-reviewed
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ACTA HISTOCHEMICA ET CYTOCHEMICA, 16(2) 138-147, 1983 Peer-reviewed
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SCIENCE, 219(4580) 75-77, 1983 Peer-reviewed
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NEUROCHEMISTRY INTERNATIONAL, 5(5) 603-609, 1983 Peer-reviewed
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ACTA HISTOCHEMICA ET CYTOCHEMICA, 16(3) 245-258, 1983 Peer-reviewed
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ANALYTICAL BIOCHEMISTRY, 132(1) 183-189, 1983 Peer-reviewed
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JOURNAL OF NEUROCHEMISTRY, 40(6) 1585-1589, 1983 Peer-reviewedA new method for the measurement of tyrosine hydroxylase (TH; EC 1.14.16.2) activity in brain slices was developed by using high-performance liquid chromatography (HPLC) with electrochemical detection (ED). To estimate TH activity in brain slices containing all of the components of the enzyme system, tetrahydrobiopterin, dihydropteridine reductase, and TH itself, slices were incubated with NSD-1055, an inhibitor of aromatic L-amino acid decarboxylase, and 3,4-dihydroxyphenylalanine (DOPA) formed from endogenous tyrosine was measured using HPLC-ED. Hydroxylation of endogenous tyrosine to DOPA in striatal slices was linear up to 90 min at 37°C, and increased by incubation with 20 mM K+ to depolarize the nerve cells. Furthermore, the formation of DOPA could be detected in all parts of brain regions examined, and the activity in this slice system was nearly parallel to the maximal velocity of the homogenate from the slices as enzyme in the presence of saturating concentrations of tyrosine and 6-methyltetrahydropterin as cofactor. This assay system should be useful to study the regulatory mechanisms of TH in relatively intact tissue preparations.
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BIOCHEMICAL PHARMACOLOGY, 31(9) 1729-1734, 1982 Peer-reviewed
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CLINICAL CHEMISTRY, 28(4) 646-649, 1982 Peer-reviewed
Misc.
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JOURNAL OF NEURAL TRANSMISSION, 123(11) 1255-1278, Nov, 2016Tyrosine hydroxylase (TH), which was discovered at the National Institutes of Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines (CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of dopamine and noradrenaline in the brain stem, caused by neurodegeneration of dopamine and noradrenaline neurons, are mainly related to non-motor and motor symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1); aromatic l-amino acid decarboxylase (AADC); dopamine beta-hydroxylase (DBH); and phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD in postmortem brains from PD patients, patients with CA-related genetic diseases, mice with genetically engineered CA neurons, and animal models of PD. We purified all human CA-synthesizing enzymes, produced their antibodies for immunohistochemistry and immunoassay, and cloned all human genes, especially the human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of TH. This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as l-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.
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Catecholamine Research in the 21st Century: Abstracts and Graphical Abstracts, 10th International Catecholamine Symposium, 2012, 11-12, Dec 1, 2013
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JOURNAL OF NEUROCHEMISTRY, 123 64-64, Oct, 2012
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JOURNAL OF NEUROCHEMISTRY, 123 117-117, Oct, 2012
Books and Other Publications
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Advances in Neurology,Parkinson's Disease (Lippincott william & Wilkins, Philadelphia), 1999
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The role of catecholamine quinone species in cellular toxicity (Graham Publishing,Johnson Gty), 1999
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Advances in Neurology, Parkinson's Disease (Lippincott Williams & Wilkins, Philadelphia), 1999
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Progress in Alzheimer's and Parkinson's Diseases (Plenum Press, New York), 1998
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Progress in Alzheimer's and Parkinson's diseases (Plenum Press, New York), 1998
Professional Memberships
9Research Projects
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 2008 - 2010
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 2006 - 2007
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科学研究費助成事業, 日本学術振興会, 2000 - 2000
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 1998 - 2000
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, 1997 - 2000