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Neuronal cell death mediated by mitochondria

Research Project

Project/Area Number 21659018
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKanazawa University

Principal Investigator

YONEDA Yukio  金沢大学, 薬学系, 教授 (50094454)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,280,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2009: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsミトコンドリア / 神経細胞死 / NMDA / グルタミン酸 / 脳虚血 / NMDAレセプター / UCP2 / 人口チャネル / Ca2+蛍光イメージング / NMDA受容体 / ミトコンドリア膜電位 / ミトコンドリア内カルシウム濃度 / mPTP / 海馬神経細胞 / 細胞内遊離カルシウム濃度
Research Abstract

Glutamate neurotoxicity was found to at least in part involve mitochondrial membrane potential disruption, mPTP orchestration, mitochondrial free Ca^<2+> levels and UCP2 expression in rat hippocampal and cortical neurons. In HEK293 cells with acquired NMDAR channels and overexpressed UCP2, a more marked increase was seen in mitochondrial free Ca^<2+> levels, in addition to more severe cell death, after the exposure to NMDA than in cells without UCP2 overexpression. Accordingly, UCP2 could play a role as a determinant of the neurotoxicity mediated by NMDAR through a mechanism related to the modulation of mitochondrial free Ca^<2+> levels in neurons.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010 2009 Other

All Journal Article (40 results) (of which Peer Reviewed: 40 results) Presentation (4 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Possible involvement of mitochondrial uncoupling protein-2 in cytotoxicity mediated by acquired N-methyl-D-aspartate receptor channels2012

    • Author(s)
      Fukumori R, Takarada T, Kambe Y, Nakazato R, Fujikawa K & Yoneda Y
    • Journal Title

      Neurochem Int

      Volume: (in press) Issue: 4 Pages: 498-505

    • DOI

      10.1016/j.neuint.2012.03.019

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible modulation of process extension by N-methyl-D-aspartate receptor expressed in osteocytic MLO-Y4 cells2012

    • Author(s)
      Fujita H, Hinoi E, Nakatani E, Yamamoto T, Takarada T & Yoneda Y
    • Journal Title

      J Pharmacol Sci

      Volume: (in press)

    • NAID

      10030760551

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amelioration by the natural polyamine, spermine, of cartilage and bone destruction in rats with collagen-induced arthritis2012

    • Author(s)
      Iezaki T, Hinoi E, Yamamoto T, Ishiura R, Ogawa S & Yoneda Y
    • Journal Title

      J Pharmacol Sci

      Volume: (in press)

    • NAID

      10030760536

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Delayed Mitochondrial Membrane Potential Disruption by ATP in Cultured Rat Hippocampal Neurons Exposed to <I>N</I>-Methyl-D-Aspartate2012

    • Author(s)
      Fujikawa K, Nakamichi N, Kato S, Fukumori R, Hida M, Takarada T & YonedaY
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 119 Issue: 1 Pages: 20-29

    • DOI

      10.1254/jphs.12034FP

    • NAID

      10030760182

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts2012

    • Author(s)
      Takeshi Takarada, Mika Takarada-Iemata, Yoshifumi Takahata, Daisuke Yamada, Tomomi Yamamoto, Yukari Nakamura, Eiichi Hinoi, Yukio Yoneda
    • Journal Title

      J Cell Physiol

      Volume: (in press) Issue: 10 Pages: 3477-87

    • DOI

      10.1002/jcp.24048

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Natural polyamines spermidine and spermine prevent bone loss through preferential disturbance of osteoclastic activation in ovariectomized mice2012

    • Author(s)
      Yamamoto T, Hinoi E, Fujita H, Iezaki T, Takahata Y, Takamori M & Yoneda Y
    • Journal Title

      Br J Pharmacol

      Volume: (in press)

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Positive regulation of osteoclastic differentiation by growth differentiation factor-15 up-regulated in osteocytic cells under hypoxia2012

    • Author(s)
      Hinoi E, Ochi H, Takarada T, Nakatani E, Iezaki T, Nakajima H, Fujita H, Takahata Y, Hidano S, Kobayashi T, Takeda S & Yoneda Y
    • Journal Title

      J Bone Miner Res

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible modulation of process extension by N-methyl-D-aspartate receptor expressed in osteocytic MLO-Y4 cells2012

    • Author(s)
      Fujita H, Hinoi E
    • Journal Title

      J Pharmacol Sci

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amelioration by the natural polyamine, spermine, of cartilage and bone destruction in rats with collagen-induced arthritis2012

    • Author(s)
      Iezaki T, Hinoi E
    • Journal Title

      J Pharmacol Sci

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive regulation of osteoclastic differentiation by growth differentiation factor-15 up-regulated in osteocytic cells under hypoxia2012

    • Author(s)
      Eiichi Hinoi, Hiroki Ochi, Takeshi Takarada, Eri Nakatani, Takashi Iezaki, Hiroko Nakajima, Hiroyuki Fujita, Yoshifumi Takahata, Shinya Hidano, Takashi Kobayashi, Shu Takeda, Yukio Yoneda
    • Journal Title

      J Bone Miner Res

      Volume: 4 Issue: 4 Pages: 938-949

    • DOI

      10.1002/jbmr.1538

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells2011

    • Author(s)
      Yukary Nakamura, Noritaka Nakamichi, Takeshi Takarada, Kiyokazu Ogita, Yukio Yoneda
    • Journal Title

      Neurochem.Int.

      Volume: 60 Issue: 5 Pages: 448-457

    • DOI

      10.1016/j.neuint.2011.08.018

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] γ-aminobutyric acid, type B receptors negatively regulate osteoblast ogenesis toward disturbance of osteoclastogenesis mediated by receptor activator of nuclear factor κB ligand in mouse bone2011

    • Author(s)
      Yoshifumi Takahata, Takeshi Takarada, Eiichi Hinoi, Yukari Nakamura, Hiroyuki Fujita, Yukio Yoneda
    • Journal Title

      J Biol Chem

      Volume: 286 Issue: 38 Pages: 32906-32917

    • DOI

      10.1074/jbc.m111.253526

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective Upregulation of Per1 mRNA Expression by ATP Through Activation of P2X7 Purinergic Receptors Expressed in Microglial Cells2011

    • Author(s)
      Nakazato R, Takarada T
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 116 Issue: 4 Pages: 350-361

    • DOI

      10.1254/jphs.11069FP

    • NAID

      10029895565

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive regulation by GABABR1 subunit of leptin expression through gene transactivation in adipocytes2011

    • Author(s)
      Yukari Nakamura, Eiichi Hinoi, Takeshi Takarada, Yoshifumi Takahata, Tomomi Yamamoto, Hiroyuki Fujita, Saya Takada, Syota Hashizume, Yukio Yoneda
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 5 Pages: e20167-e20167

    • DOI

      10.1371/journal.pone.0020167

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pivotal role of mitochondrial free calcium in neurotoxicity mediated by pN-methyl-D-aspartate receptors in cultured rat hippocampal neurons.2011

    • Author(s)
      Kambe Y
    • Journal Title

      Neurochem Int

      Volume: in press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exacerbated vulnerability to oxidative stress in astrocytic C6 glioma cells with stable overexpression of the glutamine transporter slc38a12011

    • Author(s)
      Ogura M
    • Journal Title

      Neurochem Int

      Volume: 58 Pages: 501-511

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gradual downregulation of protein expression of the partner GABABR2 subunit during postnatal brain development in mice defective of GABABR1 subunit.2011

    • Author(s)
      Fukui M, Ozawa S
    • Journal Title

      J Pharmacol Sci

      Volume: 115 Pages: 45-55

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Requirement of both NR3A and NR3B subunits for dominant negative properties on Ca2+ mobilization mediated by acquired N-methyl-D-aspartate receptor channels into mitochondria.2010

    • Author(s)
      Fukumori R
    • Journal Title

      Neurochem Int

      Volume: 57 Pages: 730-737

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferential inhibition by antidiarrheic 2-methoxy-4-methylphenol of Ca^<2+> influx across acquired N-methyl-D-aspartate receptor channels composed of NR1/NR2B subunit assembly.2010

    • Author(s)
      Nakamichi N., Fukumori R., Takarada T., Kambe Y., Yamamoto T., Matsushima N., Moriguchi N., Yoneda Y.
    • Journal Title

      J.Neurosci.Res. (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induced tolerance to glutamate neurotoxicity through downregulation of NR2 subunits of N-methyl-D-aspartate receptors in cultured rat striatal neurons.2010

    • Author(s)
      Kambe Y., Nakamichi N., Takarada T., Fukumori R., Yoneda Y.
    • Journal Title

      J.Neurosci.Res. (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition by 2-methoxy-4-ethylphenol of Ca^<2+> influx through acquired and native N-methyl-D-aspartate receptor channels.2010

    • Author(s)
      Fukumori R., Nakamichi N., Takarada T., Kambe Y., Matsushima N., Moriguchi N., Yoneda Y.
    • Journal Title

      J.Pharmacol.Sci. (in press)

    • NAID

      10027744270

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ITZ-1 a client-selective Hsp90 inhibitor efficiently induces heat shock factor 1 activation.2010

    • Author(s)
      Kimura H., Yukitake H., Tajima Y., Suzuki H., Chikatsu T., Morimoto S., Funabashi Y., Omae H., Ito T., Yoneda Y., Takizawa M.
    • Journal Title

      Chemistry and Biology 17

      Pages: 18-27

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine receptor-like factor 1 is highly expressed in damaged human knee osteoarthritic cartilage and is involved in osteoarthritis downstream of TGF-β.2010

    • Author(s)
      Tsuritani K., Takeda J., Sakagami J., Ishii A., Eiksson T., Hara T., Ishibashi H., Koshihara Y., Yamada K., Yoneda Y.
    • Journal Title

      Calcif.Tissue Int. 86

      Pages: 47-57

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood.2009

    • Author(s)
      Ibi D., Nagai T., Koike H., Kitahara Y., Mizoguchi H., Niwa M., Jaaro-Peled H., Nitta A., Yoneda Y., Nabeshima T., Sawa A., Yamada K.
    • Journal Title

      Behav.Brain Res 206

      Pages: 32-37

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal, phehcyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood.2009

    • Author(s)
      Nakatani-Pawlak A., Yamaguchi K., Tatsumi Y., Mizoguchi H., Yoneda Y.
    • Journal Title

      Biol.Pharm.Bull. 32

      Pages: 1576-1583

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional induction and translational inhibition of Arc and Cugbp2 in mice hippocampus after transient global ischemia under normothermic condition.2009

    • Author(s)
      Otsuka N., Tsuritani K., Sakurai T., Kato K., Matoba R., Itoh J., Okuyama S., Yamada K., Yoneda Y.
    • Journal Title

      Brain Res. 1287

      Pages: 136-145

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interference by adrenaline with chondrogenic differentiation through suppression of gene transactivation mediated by Sox9 family members.2009

    • Author(s)
      Takarada T., Hojo H., Iemata M., Sahara., Kodama A., Nakamura N., Hinoi E., Yoneda Y.
    • Journal Title

      Bone 45

      Pages: 568-578

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A protein-protein interaction of stress-responsive myosin VI endowed to inhibit neural progenitor self-replication with RNA binding protein, TLS, in marine hippocampus.2009

    • Author(s)
      Takarada T., Tamaki K., Takumi T., Ogura M., Ito Y., Nakamichi N., Yoneda Y.
    • Journal Title

      J.Neurochem. 110

      Pages: 1457-1468

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neonatal polyl : C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood.2009

    • Author(s)
      Ibi D., Nagai T., Kitahara Y., Mizoguchi H., Koike H., Shiraki A., Takuma K., Kamei H., Noda Y., Nitta A., Nabeshima T., Yoneda Y., Yamada K.
    • Journal Title

      Neurosci.Res. 64

      Pages: 297-305

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral abnormality and pharmacologic response in social isolation-reared mice.2009

    • Author(s)
      Koike H., Ibi D., Mizoguchi H., Nagai T., Nitta A., Takuma K., Nabeshima T., Yoneda Y, Yamada K.
    • Journal Title

      Behav.Brain Res. 202

      Pages: 114-121

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurogenesis mediated by γ-aminobutyric acid and glutamate signaling.2009

    • Author(s)
      Nakamichi N., Takarada T., Yoneda Y.
    • Journal Title

      J.Pharmacol.Sci. 110

      Pages: 133-149

    • NAID

      10025736951

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interference with cellular differentiation by D-serine through antagonism at N-methyl-D-aspartate receptors composed of NR1 and NR3A subunits in chondrocytes.2009

    • Author(s)
      Takarada T., Takahata Y., Iemata M., Hinoi E., Uno K., Hirai T., Yamamoto T., Yoneda Y.
    • Journal Title

      J.Cell.Physiol. 220

      Pages: 756-764

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible promotion of neuronal differentiation in fetal rat brainneural progenitor cells after sustained exposure to static magnetism.2009

    • Author(s)
      Nakamichi N., Ishioka Y., Hirai T., Ozawa S., Tachibana M., Nakamura N., Takarada T., Yoneda Y.
    • Journal Title

      J.Neurosci.Res. 87

      Pages: 2406-2417

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes.2009

    • Author(s)
      Nakamura Y., Takarada T., Kodama A., Hinoi E., Yoneda Y.
    • Journal Title

      J.Pharmacol.Sci. 109

      Pages: 413-423

    • NAID

      10025735254

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clarithromycin prevents smoke-induced emphysema in mice.2009

    • Author(s)
      Nakanishi Y., Kobayashi D., Asano Y., Sakurai T., Kashimura M., Okuyama S., Yoneda Y., Shapiro S.D., Takayama K.
    • Journal Title

      Amer.J.Resp.Crit.Care Med. 179

      Pages: 271-278

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transactivation by runt related factor-2 of matrix metalloprotginase-13 in astrocytes.2009

    • Author(s)
      Takarada T., Yoneda Y.
    • Journal Title

      Neurosci.Lett. 451

      Pages: 99-104

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible protection by notoginsenoside R1 against neurotoxicity of N-methyl-D-aspartate receptor composed of an NRI/NT2B heteromeric assembly.2009

    • Author(s)
      Gu B., Nakamichi N., Zhang W.-S., Nakamura Y., Kambe Y., Fukumori R., Takuma K, Yamada K., Takarada T., Taniura H., Yoneda Y.
    • Journal Title

      J.Neurosci.Res. 87

      Pages: 2145-2156

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protection against kainate neurotoxicity by ginsenosides : Attenuation of convulsive behavior, mitochondrial dysfunction, and oxidative stress.2009

    • Author(s)
      Shin E.-J., Jeong J.H., Kim A.-Y., Koh Y.H., Nah S.-Y., Kim W.-K., Ko K.H., Kim H.J., Wie M.-B., Kwon Y.S., Yoneda Y., Kim H.-C.
    • Journal Title

      J.Neurosci.Res. 87

      Pages: 710-722

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tacrolimus(FK506)suppresses rt-PA-induced hemorrhagic transformation in a rat thrombotic ischemia stroke model.2009

    • Author(s)
      Maeda M., Furuichi Y., Noto T., Matsuoka N., Mutoh S., Yoneda Y.
    • Journal Title

      Brain Res. 1254

      Pages: 99-108

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional expression of beta2 adrenergic receptors responsible for protection against oxidative stress through promotion of glutathione synthesis after Nrf2 upregulation in undifferentiated mesenchymal C3H10T1/2 stem cells.2009

    • Author(s)
      Takahata Y., Takarada T., Iemata M., Yamamoto T., Nakamura Y., Kodama A., Yoneda Y.
    • Journal Title

      J.Cell.Physiol. 218

      Pages: 268-275

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Neurotoxic NMDA signals mediated by mitochondria2012

    • Author(s)
      Yoneda Y
    • Organizer
      APSN/ISNN euroscience School
    • Place of Presentation
      Tangdu Hospital, The Fourth Military Medical University(China)
    • Year and Date
      2012-02-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Neurotoxic NMDA signals mediated by mitochondria2012

    • Author(s)
      米田幸雄
    • Organizer
      APSN/ISN Neuroscience School
    • Place of Presentation
      Tangdu Hospital, The Fourth Military Medical University(中国)(招待講演)
    • Year and Date
      2012-02-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] NMDA NEUROTOXICITYMEDIATED BY MITOCHONDRIA2011

    • Author(s)
      Yoneda Y
    • Organizer
      The Glutamatergic Synapse
    • Place of Presentation
      Megaron Athens International Conference Centre(Greece)
    • Year and Date
      2011-09-02
    • Related Report
      2011 Final Research Report
  • [Presentation] NMDA NEUROTOXICITY MEDIATED BY MITOCHONDRIA2011

    • Author(s)
      米田幸雄
    • Organizer
      The Glutamatergic Synapse
    • Place of Presentation
      Megaron Athens International Conference Centre(ギリシャ)(招待講演)
    • Year and Date
      2011-09-02
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.p.kanazawa-u.ac.jp/~yakubutu/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.p.kanazawa-u.ac.jp/~yakubutu/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 神経細胞新生促進組成物2010

    • Inventor(s)
      米田幸雄,宝田剛志,川越博文
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Number
      2010-254320
    • Filing Date
      2010-11-12
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 神經細胞新生促進租成物2010

    • Inventor(s)
      米田幸雄, 宝田剛志, 川越博文
    • Industrial Property Rights Holder
      金沢大学
    • Industrial Property Number
      2010-254320
    • Filing Date
      2010-11-12
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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