Biography:

In the past Akira Ishii has collaborated on articles with Hajime Takizawa and Sakae Arimoto. One of their most recent publications is A selective Ca2+calmodulin-dependent protein kinase II inhibitor, KN-62, inhibits the enhanced phosphorylation and the activation of tyrosine hydroxylase by 56 mM K+ in rat pheochromocytoma PC12h cells. Which was published in journal Biochemical and Biophysical Research Communications.

More information about Akira Ishii research including statistics on their citations can be found on their Copernicus Academic profile page.

Akira Ishii's Articles: (48)

A selective Ca2+calmodulin-dependent protein kinase II inhibitor, KN-62, inhibits the enhanced phosphorylation and the activation of tyrosine hydroxylase by 56 mM K+ in rat pheochromocytoma PC12h cells

AbstractInvolvement of Ca2+calmodulin-dependent protein kinase II (Ca2+CaM-kinase II) on the phosphorylation of tyrosine hydroxylase (TH, EC.1.14.16.2) in rat pheochromocytoma, PC12h cells was examined using KN-62, 1-[N,O-Bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, a selective inhibitor of Ca2+CaM-kinase II. Both the enhanced phosphorylation of TH and the activated l-3,4-dihydroxyphenylalanine (DOPA) formation in the high K+ depolarization were inhibited by 10 μM KN-62. After incubation of PC12h cells with 10 μM KN-62 for 1 hr, the activation of TH with 3 min incubation of 56 mM K+ was reduced to the basal activity. However, KN-62 did not directly affect the activity of purified rat TH at pH 6.0 or 7.0. These results indicate that Ca2+CaM-kinase II phosphorylates and activates TH of PC12h cells in the high K+ depolarization.

Interleukin 6B cell stimulatory factor-II is expressed and released by normal and transformed human bronchial epithelial cells

AbstractAirway epithelial cells have a potential to participate in local immune and inflammatory responses via releasing biologically active compounds. We studied the expression and release of interleukin 6 (IL-6), a multifunctional cytokine possibly involved in tissue immune responses. Primary culture of normal human bronchial epithelial cells and its transformed cell line BEAS-2B released significant amount of biologically and immunologically intact IL-6 into media. A protein synthesis inhibitor cycloheximide abolished the IL-6 release, suggesting a de novo synthesis. Northern blot analysis demonstrated the expression of the specific IL-6 mRNA. Human bronchial epithelial cells can produce IL-6 and contribute to the local activity of IL-6, suggesting that these cells may play a role in the regulation of airway immune responses.

A selective Ca2+calmodulin-dependent protein kinase II inhibitor, KN-62, inhibits the enhanced phosphorylation and the activation of tyrosine hydroxylase by 56 mM K+ in rat pheochromocytoma PC12h cells

AbstractInvolvement of Ca2+calmodulin-dependent protein kinase II (Ca2+CaM-kinase II) on the phosphorylation of tyrosine hydroxylase (TH, EC.1.14.16.2) in rat pheochromocytoma, PC12h cells was examined using KN-62, 1-[N,O-Bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, a selective inhibitor of Ca2+CaM-kinase II. Both the enhanced phosphorylation of TH and the activated l-3,4-dihydroxyphenylalanine (DOPA) formation in the high K+ depolarization were inhibited by 10 μM KN-62. After incubation of PC12h cells with 10 μM KN-62 for 1 hr, the activation of TH with 3 min incubation of 56 mM K+ was reduced to the basal activity. However, KN-62 did not directly affect the activity of purified rat TH at pH 6.0 or 7.0. These results indicate that Ca2+CaM-kinase II phosphorylates and activates TH of PC12h cells in the high K+ depolarization.

Interleukin 6B cell stimulatory factor-II is expressed and released by normal and transformed human bronchial epithelial cells

AbstractAirway epithelial cells have a potential to participate in local immune and inflammatory responses via releasing biologically active compounds. We studied the expression and release of interleukin 6 (IL-6), a multifunctional cytokine possibly involved in tissue immune responses. Primary culture of normal human bronchial epithelial cells and its transformed cell line BEAS-2B released significant amount of biologically and immunologically intact IL-6 into media. A protein synthesis inhibitor cycloheximide abolished the IL-6 release, suggesting a de novo synthesis. Northern blot analysis demonstrated the expression of the specific IL-6 mRNA. Human bronchial epithelial cells can produce IL-6 and contribute to the local activity of IL-6, suggesting that these cells may play a role in the regulation of airway immune responses.

Evaluation of the mutagenicity and the tumor-promoting activity of parasite extracts: Schistosoma japonicum and Clonorchis sinensis

AbstractIn relation to the observed association of carcinogenesis with parasitic infections, the mutagenicity of extracts of Schistosoma japonicum and Clonorchis sinensis was examined. In the bacterial mutagenicity tests using the Ames Salmonella typhimurium strains TA98, TA100, TA97 and TA102, and Escherichia coli WP2 and WP2 uvrA pKM101 Schistosoma soluble egg antigen and a homogenate of adult Schistosoma worms showed no positive responses either in the presence or in the absence of S9 mix. Likewise, adult worm extracts of Clonorchis showed no mutagenicity. The Schistosoma soluble egg antigen showed a weak but significant activity for the induction of Epstein-Barr virus expression in viral genome-carrying human lymphoblastoid cells in culture. This phenomenon suggests that the soluble egg antigen possesses tumor-promoting activity.

Modified metabolism of a carcinogen, 3-amino-1-methy-5H-pyrido[4,3-b]indole (Trp-P-2), by liver S9 from Schistosoma japonicum-infected mice

Abstractschitosoma japonicum infection has been associated with an increased incidence of liver and colorectal cancers in humans. To explore the mechanisms underlying this association, we investigated the carcinogen-metabolizing properties of liver S9 preparations from S. japonicum-infected mice and compared then with those of S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5H-pyridol[4,3-b]indole (Trp-P-2) was incubated with these S9s and the products were analyzed by high-performance liquid chromatography, we observed that the S9 from infected mice had a lower ability to convert Trp-P-2 into 30-hydroxyamino-1-methyl-5H-pyridol[4,3-b]indole (Trp-2(NHOH)), an activated form of promutagenic Trp-P-2, than the S9 from uninfected mice. We found that both of these S9 preparations have a high ability to reduce Trp-P-2(NHOH) into Trp-P-2; however, the infected-mouse S9 showed a significantly greater reducing power than the control S9. This difference appears to be responsible for the observed lower mutagen-activating potential of the infected mouse S9. These results suggest that hepatic enzyme activities of S. japonicum-infected mice are quantitatively different from those of normal mice.

Theory of ion desorption spectroscopy stimulated by positrinium formation at a solid surface

AbstractA theory of ion desorption due to positrium formation with an electron of an adsorbate at a surface is presented. As an example, a calculation is performed for a hydrogen atom on a Si(100)2 × 1 surface; this gives a cross section that is 108 times larger than for photo-stimulated desorption. Since the cross section depends strongly on the incident positron energy, we can use it as a spectroscopic technique similar to that of diffuse LEED to determine the atomic structure of randomly adsorbed atoms or molecules on the crystal surface.

Effect of (6R)- and (6S)-tetrahydrobiopterin on L-3,4-dihydroxyphenylalanine (DOPA) formation in NRK fibroblasts transfected with human tyrosine hydroxylase type 2 cDNA

Abstractl-erythro-5,6,7,8-Tetrahydrobiopterin (BH4), which is the cofactor of aromatic amino acid hydroxylases, plays an important role in the biosyntheses of monoamine neurotransmitters. BH4 exists as natural (6R)- and unnatural (6S)-isomers. In our previous reports, only (6R)-isomer significantly stimulated cofactor activity for tyrosine, tryptophan and phenylalanine hydroxylases (TH, TPH, PAH) in whole animals or in tissue slices. In this study we have compared the in situ cofactor activity on TH between natural (6R)- and unnatural (6S)-isomers in clonal cells. We have transfected human TH type 2 cDNA into the normal rat kidney (NRK) fibroblasts. These cells expressed TH protein, but had neither DOPA decarboxylase (DDC) nor BH4. Thus, TH activity was observed only in the presence of exogenous BH4. We compared the difference in in situ DOPA formation by TH activity in the presence of (6R)- or (6S)-BH4 in the human TH-transfected cells. The effect of exogenous BH4 was also compared between (6R)- and (6S)-isomers in rat pheochromocytoma PC12h cells, which contained approximately 100 μM endogenous (6R)-BH4. The rate of uptake of both BH4 isomers into these cells increased in proportion to the pterin cofactor concentrations in the incubation medium up to 400 μM but was nearly saturated at 1 mM BH4. TH-transfected NRK fibroblasts formed DOPA only in the presence of exogenously added (6R)- or (6S)-BH4 dose-dependently and released DOPA into the medium. At a saturating concentration of 1 mM, (6R)-BH4 was approximately three times as active as (6S)-BH4. In contrast, in PC12h cells which contained endogenous (6R)-BH4 (approximately 100 μM), exogenous (6R)-BH4 activated DOPA formation maximally at 500 μM about 10-fold, while (6S)-BH4 activated it only slightly, about 2.5-fold. These results suggest that (6S)-isomer has lower cofactor activity with TH in the cells than (6R)-isomer. This TH transfected fibroblasts should be useful to assess cofactor activities of tetrahydropteridines in the cell.

Ferrous ion activates the less active form of human adrenal tyrosine hydroxylase☆

AbstractThe less active form of human tyrosine hydroxylase has been previously reported but its physiological role is unknown. We partially purified the less active form of tyrosine hydroxylase from human adrenals, and examined differences in the properties of the active and less active forms. We succeeded in activation of the less active form of human tyrosine hydroxylase by addition of 100 μM Fe2+. Fe2+ decreased the Kmax for pteridine cofactor in both the active and less active forms, but increased the Vmax only in the less active form. Fe2+ changed the Vmax but not the Km of the less active form for tyrosine. These results suggest that Fe2+ may regulate tyrosine hydroxylase activity in vivo as a result of activation of its less active form.

Photophysical processes of pyrene adsorbed onto porous glasses. Importance of evacuation temperature

AbstractThe effect of the evacuation temperature used to remove residual solvent (cyclohexane) on the fluorescence spectrum and fluorescence decay curve of pyrene adsorbed on porous glass (average diameters, 40 Å and 300 Å; PG40 and PG300) was investigated. The “growing-in” phenomenon in the initial stage of the decay curve was observed for PG300 evacuated at temperatures (338 K) lower than the boiling temperature of cyclohexane (353 K). However, this phenomenon was not observed for PG300 evacuated at temperatures (373 K) higher than the boiling temperature of cyclohexane and for all PG40 specimens. Thus the evacuation temperature after adsorption plays an important role in the photophysical properties of pyrene molecules and determines whether or not they form excimer-like conformations of the surfaces.

Influence of pore size on the intensity of the monomer and excimer-like fluorescence of pyrene adsorbed onto porous glasses

AbstractThe influence of the pore size of calcinated (773 K) porous glasses (average pore diameters, 40, 80 and 300 Å) on the ratio R of the emission intensity of the excimer-like fluorescence to that of the monomer fluorescence of pyrene adsorbed on porous glass was examined. R decreased with increasing pore size. The results were interpreted on the basis of the photophysical processes of adsorbed pyrene molecules on the surfaces. The ratio of the quantum efficiency for excimer formation from excited dimeric pyrene was estimated to be 1:0.23:0.11 for PG40, PG80 and PG300. The fractal nature of the surfaces of the individual porous glasses played an important role in the photophysical processes of pyrene encapsulated in the pores.

Rapid analysis of pentazocine in human plasma by liquid chromatography/mass spectrometry with sonic spray ionization

AbstractA rapid determination method for pentazocine in human plasma without complicated pretreatments has been constructed by liquid chromatography/mass spectrometry (LC/MS) with sonic spray ionization (SSI) using an Oasis HLB cartridge column. The reliability on our method was investigated for human plasma samples spiked with pentazocine and dextromethorphan as internal standard. The regression equation for pentazocine showed good linearity in the ranges of 30–1,250 and 1,250–10,000 ng ml−1; the detection limit was 19.5 ng ml−1 in human plasma. The sensitivity, accuracy and precision were satisfactory to quantify the wide range of therapeutic to toxic levels. Our method established enabled the determination of a single sample of pentazocine in human plasma only within 4 min, and allowed analysis of more than 100 samples per day. The present method seems applicable for actual cases encountered in the forensic and clinical practices.

Original articleMutation screening of the muscarinic m2 and m3 receptor genes in asthmatics, outgrow subjects, and normal controls

AbstractMuscarinic receptors are important in the development of airway hyperresponsiveness. In some patients with asthma and in animal models of hyperreactivity, functional abnormalities in these receptors are suggested to contribute to disease. Here, we have screened for single nucleotide polymorphisms in the coding region of human muscarinic m2 and m3 receptor genes using direct fluorescence sequencing. DNA samples from 102 current asthmatics and 58 who had outgrown asthma (“outgrow” patients) were compared with 70 random non-asthmatic controls. A mutation characterized by a single base substitution (A1050G, Ser350Ser) was identified in the muscarinic m2 receptor gene. This polymorphism was common and was represented in all three groups studied. In contrast, in the m3 receptor coding region examined, we found a very rare nucleotide variant (C261T, Ile87Ile), identified in only one of the 230 samples genotyped. Therefore, neither A1050G in the m2 receptor nor C261T in the m3 receptor is likely to be functionally significant for airway hyperresponsiveness in asthma. Our data suggest that both the m2 and m3 receptor genes are highly conserved, and no significant genetic mutations are related to their possible functional changes in human asthma.

Regular ArticleCharacterization and Identification of Exflagellation-Inducing Factor in the Salivary Gland of Anopheles stephensi (Diptera: Culicidae)

AbstractGamete activation factor (GAF) induces exflagellation of Plasmodium microgametes. We found GAF in the salivary glands of female mosquitoes, Anopheles stephensi. The exflagellation was induced in a concentration-dependent manner in the supernatant of salivary gland's crude homogenate. The exflagellation-inducing activity in the salivary gland was higher than that in the midgut and the head. GAF in the salivary glands was found to be heat stable and low molecular weight (<3000 molecular weight). Analysis of the supernatant by capillary electrophoresis and UV absorbance profile showed that the salivary glands contained xanthurenic acid, which was previously identified as GAF in the head of A. stephensi. The exflagellation-inducing activity in the salivary gland declined immediately after a blood meal, implying that GAF was in the saliva, and was delivered into the midgut together with the blood and induced exflagellation in the midgut.

Research ReportNeural substrates activated by viewing others expressing fatigue: A magnetoencephalography study

AbstractThe neural substrates of the fatigue sensation have not been totally identified. Several lines of evidence demonstrate that seeing emotional changes in others activates brain regions involved in experiencing similar emotions. We hypothesized that there exists a mirror system regarding the fatigue sensation and that brain regions associated with the fatigue sensation may be activated by viewing other individuals expressing fatigue. In this study, we attempted to identify the neural substrates activated by viewing other fatigued individuals using magnetoencephalography (MEG). Twelve healthy participants were enrolled in our study after providing written informed consent. During MEG recordings, they viewed a set of pictures projected on a screen. The pictures, which were presented in a randomized order, were of a person with a fatigued or neutral facial expression. When participants viewed pictures of people with fatigued expressions, we were able to estimate equivalent current dipoles (ECDs) in the posterior cingulate cortex (PCC) in 9 of 12 participants approximately 300 ms after the onset of each picture presentation. When they viewed pictures of people with neutral expressions, we were not able to estimate corresponding ECDs for any participant. The PCC is the brain region activated by viewing others expressing fatigue, suggesting existence of the shared neural substrates of felt and observed fatigue.

Research ReportNeural effects of prolonged mental fatigue: A magnetoencephalography study

Highlights•It is important to understand the neural mechanisms of mental fatigue.•We quantified the neural effect of a long-duration mental fatigue-inducing task.•Magnetoencephalography was used to examine the neural activities.•Overactivation of the visual cortex caused by the task trials was observed.•Our results increase understanding of the neural mechanisms of mental fatigue.

Research ReportNeural mechanism of central inhibition during physical fatigue: A magnetoencephalography study

Highlights•We tried to clarify the neural mechanism of central inhibition during physical fatigue.•In the right dorsolateral prefrontal cortex, the alpha-band event-related desynchronization was identified.•The event-related desynchronization level was positively associated with the subjective level of right hand fatigue.•We demonstrated that the right dorsolateral prefrontal cortex is involved in the neural substrates of central inhibition.

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