Author Asanuma, Masato| Miyazaki, Ikuko| Francisco J., Diaz-Corrales| Higashi, Youichirou| Namba, Masayoshi| Ogawa, Norio|
Published Date 2013-06-12
Publication Title PLOS ONE
Volume volume8
Issue issue6
Content Type Journal Article
JaLCDOI 10.18926/AMO/53020
FullText URL 68_6_317.pdf
Author Kasahara, Kyosuke| Miyoshi, Ko| Murakami, Shinki| Miyazaki, Ikuko| Asanuma, Masato|
Abstract In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain.
Keywords primary cilia astrocyte ADP-ribosylation factor-like protein 13B
Amo Type Original Article
Published Date 2014-12
Publication Title Acta Medica Okayama
Volume volume68
Issue issue6
Publisher Okayama University Medical School
Start Page 317
End Page 322
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25519025
Web of Sience KeyUT 000346882200001
Author Murakami, Shinki| Miyazaki, Ikuko| Sogawa, Norio| Miyoshi, Ko| Asanuma, Masato|
Published Date 2014-10
Publication Title Neurotoxicity Research
Volume volume26
Issue issue3
Content Type Journal Article
JaLCDOI 10.18926/AMO/47009
FullText URL 65_5_279.pdf
Author Miyoshi, Ko| Kasahara, Kyosuke| Miyazaki, Ikuko| Asanuma, Masato|
Abstract Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.
Keywords primary cilium length lithium cyclic AMP soluble tubulin intraflagellar transport
Amo Type Review
Published Date 2011-10
Publication Title Acta Medica Okayama
Volume volume65
Issue issue5
Publisher Okayama University Medical School
Start Page 279
End Page 285
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22037264
Web of Sience KeyUT 000296116400001
JaLCDOI 10.18926/AMO/40129
FullText URL 64_4_219.pdf
Author Doi, Maho| Miyazaki, Ikuko| Nagamachi, Tomoko| Shinomiya, Kazuaki| Matsunaga, Hisashi| Sendo, Toshiaki| Kawasaki, Hiromu| Asanuma, Masato| Gomita, Yutaka| Kitamura, Yoshihisa|
Abstract We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.
Keywords ACTH imipramine lithium proliferation Ki-67
Amo Type Original Article
Published Date 2010-08
Publication Title Acta Medica Okayama
Volume volume64
Issue issue4
Publisher Okayama University Medical School
Start Page 219
End Page 223
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 20802538
Web of Sience KeyUT 000281384400002
JaLCDOI 10.18926/AMO/32278
FullText URL fulltext.pdf
Author Tanaka, Ken-ichi| Fujita, Naoko| Asanuma, Masato| Ogawa, Norio|
Abstract <p>We examined the effects of FK506 and its non-immunosuppressive derivative, GPI1046, on H2O2-induced reduction of cell viability and apoptotic cell death in Neuro 2A cells. Our results suggest that the protective properties of GPI1046 against H2O2-induced reduction of cell viability are equipotent with those of FK506 and may be mediated by increased intracellular concentrations of glutathione (GSH). In addition, both FK506 and GPI1046 prevented apoptotic cell death in Neuro 2A cells, although the antiapoptotic effect of FK506 was somewhat stronger than that of GPI1046. These findings suggest that non-immunosuppressive immunophilin ligands such as GPI1046 might be potentially useful in treatment of neurodegenerative diseases without serious side effects such as immune deficiency.</p>
Keywords hydrogen peroxide immunophilin ligands apoptosis glutathione FK506 GPI1046
Amo Type Article
Published Date 2000-12
Publication Title Acta Medica Okayama
Volume volume54
Issue issue6
Publisher Okayama University Medical School
Start Page 275
End Page 280
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11132921
Web of Sience KeyUT 000166042900006
JaLCDOI 10.18926/AMO/32199
FullText URL fulltext.pdf
Author Takayama, Haruhiko| Ogawa, Norio| Asanuma, Masato| Hirata, Hiroshi| Ogura, Toshio| Ota, Zensuke|
Abstract <p>To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.</p>
Keywords ?-blocker opioid receptor membrane stabilizing activity sodium index
Amo Type Article
Published Date 1991-10
Publication Title Acta Medica Okayama
Volume volume45
Issue issue5
Publisher Okayama University Medical School
Start Page 295
End Page 299
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1684486
Web of Sience KeyUT A1991GN53800001
JaLCDOI 10.18926/AMO/32105
FullText URL fulltext.pdf
Author Asanuma, Masato| Miyazaki, Ikuko| Diaz-Corrales, Francisco J| Ogawa, Norio|
Abstract <p>Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuron-specific degeneration in the substantia nigra. A number of gene mutations and deletions have been reported to play a role in the pathogenesis of familial PD. Moreover, a number of pathological and pharmacological studies on sporadic PD and dopaminergic neurotoxin-induced parkinsonism have hypothesized that mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system all play important roles in the pathogenesis and progress of PD. However, these hypotheses do not yet fully explain the mechanisms of dopaminergic neuron-specific cell loss in PD. Recently, the neurotoxicity of dopamine quinone formation by auto-oxidation of dopamine has been shown to cause specific cell death of dopaminergic neurons in the pathogenesis of sporadic PD and dopaminergic neurotoxin-induced parkinsonism. Furthermore, this quinone formation is closely linked to other representative hypotheses in the pathogenesis of PD. In this article, we mainly review recent studies on the neurotoxicity of quinone formation as a dopaminergic neuron-specific oxidative stress and its role in the etiology of PD, in addition to several neuroprotective approaches against dopamine quinone-induced toxicity.</p>
Keywords dopamine quinone quinoprotein Parkinson’sdisease oxidative stress neurotoxin
Amo Type Article
Published Date 2004-10
Publication Title Acta Medica Okayama
Volume volume58
Issue issue5
Publisher Okayama University Medical School
Start Page 221
End Page 233
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 15666991
Web of Sience KeyUT 000224708800001
JaLCDOI 10.18926/AMO/32031
FullText URL fulltext.pdf
Author Aoki, Sogawa Chiharu| Asanuma, Masato| Sogawa, Norio| Miyazaki, Ikuko| Nakanishi, Tohru| Furuta, Hiroaki| Ogawa, Noriko|
Abstract <p>The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the first of these proteins was discovered nearly 40 years ago, their functional significance remains obscure. Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously expressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominantly in the brain, and characterized as a central nervous system-specific isomer. The role of MTs in the central nervous system has become an intense focus of scientific research. An isomer of MTs, MT-III, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases. MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders.</p>
Keywords neuroprotectin metal transport localization gene expression neurodegenerative disease
Amo Type Review
Published Date 2001-02
Publication Title Acta Medica Okayama
Volume volume55
Issue issue1
Publisher Okayama University Medical School
Start Page 1
End Page 9
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11246971
Web of Sience KeyUT 000167249900001
JaLCDOI 10.18926/AMO/30980
FullText URL fulltext.pdf
Author Miyazaki, Ikuko| Asanuma, Masato|
Abstract <p>Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons.</p>
Keywords dopamine quinone quinoprotein methamphetamine Parkinson?s disease L-DOPA
Amo Type Review
Published Date 2008-06
Publication Title Acta Medica Okayama
Volume volume62
Issue issue3
Publisher Okayama University Medical School
Start Page 141
End Page 150
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 18596830
Web of Sience KeyUT 000257130300001
JaLCDOI 10.18926/AMO/30724
FullText URL Fulltext.pdf erratum_61_2_121.pdf
Author Fujita, Osamu| Asanuma, Masato| Yokoyama, Teruhiko| Miyazaki, Ikuko| Ogawa, Norio| Kumon, Hiromi|
Abstract We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness 1 week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between > or = 2.0 and < or = 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (1 Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy.
Keywords benign prostatic hyperplasia bladder outlet obstruction bladder smooth muscle signal transducer and activator of transcription 3 (STAT3) small interfering RNA (siRNA)
Amo Type Original Article
Published Date 2006-12
Publication Title Acta Medica Okayama
Volume volume60
Issue issue6
Publisher Okayama University Medical School
Start Page 299
End Page 309
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 17189973
Web of Sience KeyUT 000243019000001
Author Miyazaki, Ikuko| Asanuma, Masato| Francisco J. Diaz-Corrales| Miyoshi, Ko| Ogawa, Norio|
Published Date 2008-01-04
Publication Title 岡山医学会雑誌
Volume volume119
Issue issue3
Content Type Journal Article
Author 淺沼 幹人|
Published Date 1992-03-31
Publication Title
Content Type Thesis or Dissertation