Study on pathophysiological roles of brain NO-NCX signal

• Project/Area Number: 23390139
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Osaka University
• Principal Investigator: MATSUDA Toshio 大阪大学, 薬学研究科(研究院), 教授 (00107103)
• Co-Investigator(Kenkyū-buntansha): 吾郷 由希夫 大阪大学, 薬学研究科, 大阪大学 (50403027) ; TAKUMA Kazuhiro 大阪大学, 薬学研究科, 准教授 (90289025)
• Research Collaborator: HASHIMOTO Hitoshi 大阪大学, 薬学研究科, 教授 (30240849)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: Na+/Ca2+交換系 / 一酸化窒素 / 環境要因 / 一酸化窒素（NO） / 細胞障害 / 精神機能 / Na+/Ca2+交換系(NCX) / Nitric oxide (NO) / SEA0400 / ドパミン

Research Abstract

This study examined the role of the predominant brain-specific NCX splice variant NCX1.5 in NO-induced cytotoxicity in HEK293 cell expression system. Transfection with a plasmid construct pcDNA3.1/V5-His containing full-length rat NCX1.5 cDNA into HEK293 cells increased prominently the protein level of NCX1.5 tagged with C-terminal V5 and (His)6 epitopes (NCX1.5-V5/His). There was no difference in the cytotoxic effects by sodium nitroprusside and S-nitroso-N-acetylpenicillamine between the control and transfected cells. These results suggest that NO cytotoxicity is not dependent on NCX1.5. Microdialysis study showed that NO did not affect monoamine release in the brain. Furthermore, RT-PCR analysis showed that environmental factors did not affect the expression of NCX.

Research Products

• [Journal Article] The effect of high [K+]o on spontaneous Ca2+ waves in freshly isolated interstitial cells of Cajal from the rabbit urethra (2014)
  • Author(s): Drumm BT, Sergeant GP, Hollywood MA, Thornbury KT, Matsuda T, Baba A, Harvey BJ, McHale NG
  • Journal Title: Physiol Rep Volume: 2(1)
  • Peer Reviewed
• [Journal Article] Effect of Overexpression of the Brain-Specific Na+/Ca2+ Exchanger Splice Variant NCX1.5 on NO Cytotoxicity in HEK293 Cells (2013)
  • Author(s): Ota Y, Kawanai T, Watanabe R, Nishimura A, Ago Y, Takuma K, Matsuda T
  • Journal Title: J Pharmacol Sci Volume: 121(4) Pages: 351-354
  • NAID: 10031171147
  • Peer Reviewed
• [Journal Article] Effects of SEA0400 on Arrhythmogenicity in a Langendorff- perfused 1-month myocardial infarc- tion rabbit model (2013)
  • Author(s): Chou CC, Chang PC, Wen MS, Lee HL, Chu Y, Baba A, Matsuda T, Yeh SJ, Wu D
  • Journal Title: Pacing Clin Electro- physiol Volume: 36(5) Pages: 596-606
  • Peer Reviewed
• [Journal Article] Pretreatment of donor islets with the Na+/Ca2+ exchanger inhibitor improves the efficiency of islet transplantation (2013)
  • Author(s): Mera T, Itoh T, Kita S, Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y
  • Journal Title: Am J Transplant Volume: 13(8) Pages: 2154-2160
  • Peer Reviewed
• [Journal Article] Stimulation of Na+/H+ exchanger isoform 1 promotes microglial migration (2013)
  • Author(s): Shi Y, Yuan H, Kim D, Chanana V, Baba A, Matsuda T, Cengiz P, Ferrazzano P, Sun D
  • Journal Title: PLoS One Volume: 8(8)
  • Peer Reviewed
• [Journal Article] The glial sodium-calcium exchanger : a new target for nitric oxide-mediated cellular toxicity (2013)
  • Author(s): Takuma K, Ago Y, Matsuda T
  • Journal Title: Curr Protein Pept Sci Volume: 14 Pages: 43-50
  • Peer Reviewed
• [Journal Article] グリア細胞Na+/Ca2+交換系の病態生理学的役割 (2013)
  • Author(s): 田熊一敞, 吾郷由希夫, 松田敏夫
  • Journal Title: 生体の科学(医学書院) Volume: 64(5) Pages: 384-385
• [Journal Article] Pretreatment of donor islets with the Na(+) /Ca(2+) exchanger inhibitor improves the efficiency of islet transplantation (2013)
  • Author(s): Mera T, Itoh T, Kita S, Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y.
  • Journal Title: Am J Transplant Volume: 13 Issue: 8 Pages: 2154-2160
  • DOI: 10.1111/ajt.12306
  • Peer Reviewed
• [Journal Article] he glial sodium-calcium exchanger: a new target for nitric oxide-mediated cellular toxicity (2013)
  • Author(s): Takuma K, Ago Y, Matsuda T.
  • Journal Title: Curr Protein Pept Sci Volume: 14 Pages: 43-50
• [Journal Article] グリア細胞Na+/Ca2+交換系の病態生理学的役割 (2013)
  • Author(s): 田熊一敞，吾郷由希夫，松田敏夫
  • Journal Title: 生体の科学 Volume: 64 Pages: 384-385
• [Journal Article] Effect of Overexpression of the Brain-Specific Na+/Ca2+ Exchanger Splice Variant NCX1.5 on NO Cytotoxicity in HEK293 Cells (2013)
  • Author(s): Ota Y, Kawanai T, Watanabe R, Nishimura A, Ago Y, Takuma K, Matsuda T.
  • Journal Title: J Pharmacol Sci Volume: 121 Pages: 351-354
  • NAID: 10031171147
• [Journal Article] The glial sodium-calcium exchanger: a new target for nitric oxide-mediated cellular toxicity (2013)
  • Author(s): Takuma K, Ago Y, Matsuda T
  • Journal Title: Curr Protein Pept Sci Volume: 14 Pages: 43-50
• [Journal Article] Effect of Overexpression of the Brain-Specific Na+/Ca2+ Exchanger Splice Variant NCX1.5 on NO Cytotoxicity in HEK293 Cells (2013)
  • Author(s): Ota Y, Kawanai T, Watanabe R, Nishimura A, Ago Y, Takuma K, Matsuda T
  • Journal Title: J. Pharmacol. Sci. Volume: 121 Pages: 351-354
  • NAID: 10031171147
• [Journal Article] Neuronal nitric oxide synthase inhibition attenuates the development of L-DOPA-induced dyskinesia in hemi-Parkinsonian rats (2012)
  • Author(s): Takuma K, Tanaka T, Takahashi T, Hiramatsu N, Ota Y, Ago Y, Matsuda T
  • Journal Title: Eur J Pharmacol Volume: 683(1-3) Pages: 166-173
  • Peer Reviewed
• [Journal Article] Astrocytes modulate neural network activity by Ca² -dependent uptake of extracellular K (2012)
  • Author(s): Wang F, Smith NA, Xu Q, Fujita T, Baba A, Matsuda T, Takano T, Bekar L, Nedergaard M
  • Journal Title: Sci Signal Volume: 5(218) Pages: 26-26
  • Peer Reviewed
• [Journal Article] Revisiting the Ionic Mechanisms of Early Afterdepolarizations in Cardiomyo- cytes : Predominant by Ca Waves or Ca Currents? (2012)
  • Author(s): Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie LH
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 302(8)
  • Peer Reviewed
• [Journal Article] Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production (2012)
  • Author(s): Pandit MM, Strait KA, Matsuda T, Kohan DE
  • Journal Title: Am J Physiol Renal Physiol Volume: 302(10)
  • Peer Reviewed
• [Journal Article] Inhibition of the sodium-calcium exchanger via SEA0400 altered manganese-induced T(1) changes in isolated perfused rat hearts (2012)
  • Author(s): Chen Y, Payne K, Perara VS, Huang S, Baba A, Matsuda T, Yu X
  • Journal Title: NMR Biomed Volume: 25(11) Pages: 1280-1285
  • Peer Reviewed
• [Journal Article] New experimental evidence for mechanism of arrhythmogenic membrane potential alternans based on balance of electrogenic INCX/ICa currents (2012)
  • Author(s): Wan X, Cutler M, Song Z, Karma A, Matsuda T, Baba A, Rosenbaum DS
  • Journal Title: Heart Rhythm Volume: 9(10) Pages: 1698-705
  • Peer Reviewed
• [Journal Article] Preferential involvement of Na+/Ca2+ exchanger type-1 in the brain damage caused by transient focal cerebral ischemia in mice (2012)
  • Author(s): Morimoto N, Kita S, Shimazawa M, Namimatsu H, Tsuruma K, Hayakawa K, Mishima K, Egashira N, Iyoda T, Horie I, Gotoh Y, Iwasaki K, Fujiwara M, Matsuda T, Baba A, Komuro I, Horie K, Takeda J, Iwamoto T, Hara H
  • Journal Title: Biochem Biophys Res Commun Volume: 429(3-4) Pages: 186-190
  • Peer Reviewed
• [Journal Article] SEA0400, a specific Na+/Ca2+ exchange inhibitor, prevents dopaminergic neurotoxicity in an MPTP mouse model of Parkinson's disease (2011)
  • Author(s): Ago Y, Kawasaki T, Nashida T, Ota Y, Cong Y, Kitamoto M, Takahashi T, Takuma K, Matsuda T
  • Journal Title: Neuropharmacology Volume: 61(8) Pages: 1441-1451
  • Peer Reviewed
• [Journal Article] Ca2+ influx through reverse-mode Na+/Ca2+ exchange is critical for vascular endothelial growth factor (VEGF) mediated - ERK1/2 activation and angiogenic functions of human endothelial cells (2011)
  • Author(s): Andrikopoulos P, Baba A, Matsuda T, Djamgoz MB, Yaqoob MM, Eccles SA
  • Journal Title: J Biol Chem Volume: 286(44) Pages: 37919-37931
  • Peer Reviewed
• [Journal Article] The specific Na^+/Ca^<2+> exchange inhibitor SEA0400 prevents nitric oxide-induced cytotoxicity in SH-SY5Y cells (2011)
  • Author(s): Nashida T, et al
  • Journal Title: Neurochem.Int. Volume: 59 Pages: 51-58
  • Peer Reviewed
• [Journal Article] SEA0400, a specific Na^+/Ca^<2+> exchange inhibitor, prevents dopaminergic neurotoxicity in an MPTP mouse model of Parkinson's disease (2011)
  • Author(s): Ago Y, et al
  • Journal Title: Neuropharmacology Volume: 61 Pages: 1441-1451
  • Peer Reviewed
• [Journal Article] The Na^+/Ca^<2+>-exchanger : An essential component in the mechanism governing cardiac steroid-induced slow Ca^<2+> oscillations (2011)
  • Author(s): Feldmann T, et al
  • Journal Title: Cell Calcium Volume: 50 Pages: 424-432
  • Peer Reviewed
• [Journal Article] Ca^<2+> influx through reverse-mode Na^+/Ca^<2+> exchange is critical for vascular endothelial growth factor (VEGF) mediated-ERK1/2 activation and angiogenic functions of human endothelial cells (2011)
  • Author(s): Andrikopoulos P, et al
  • Journal Title: J.Biol.Chem. Volume: 286 Pages: 37919-37931
  • Peer Reviewed
• [Journal Article] Indirectly Probing Ca^<2+> Handling Alterations Following Myocardial Infarction in a Murine Model Using T1-Mapping Manganese-Enhanced Magnetic Resonance Imaging (2011)
  • Author(s): Waghorn B, et al
  • Journal Title: Magn.Reson.Med. Volume: 65 Pages: 239-249
  • Peer Reviewed
• [Presentation] 過密飼育環境の夜間負荷による発育期マウス精神機能の変化 (2014)
  • Author(s): 田中辰典, 吾郷由希夫, 井本絵実奈, 北本真理, 太田友樹, 田熊一敞, 松田敏夫
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] PACAP 遺伝子欠損マウスの異常行動に対する自発運動の作用 (2013)
  • Author(s): 中川 光, 福山留以, 山口浩史, 新谷紀人, 橋本均, 吾郷由希夫, 田熊一敞, 松田敏夫
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
• [Presentation] 発育期環境要因のマウス精神機能発達に対する作用 (2012)
  • Author(s): 田中辰典, 吾郷由希夫, 井本絵実奈, 北本真理, 田熊一敞, 松田敏夫
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-20
• [Presentation] PACAP 欠損マウスの学習記憶障害に対する豊かな環境飼育の影響 (2012)
  • Author(s): 福山留以, 竹本光佑, 中川 光, 新谷紀人, 橋本均, 吾郷由希夫, 田熊一敞, 松田敏夫
  • Organizer: 第121回日本薬理学会近畿部会
  • Place of Presentation: 徳島
  • Year and Date: 2012-06-29
• [Presentation] 6-Hydroxydopamine 神経障害ラットにおけるL-DOPA 誘発ジスキネジアの形成に対する神経型一酸化窒素合成酵素阻害薬7-nitroindazole の改善効果 (2012)
  • Author(s): 太田友樹, 田熊一敞, 高橋剛士, 吾郷由希夫, 松田敏夫
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
• [Presentation] レボドパ誘発ジスキネジア形成過程における神経型一酸化窒素合成酵素の役割 (2012)
  • Author(s): 田熊一敞, 田中辰典, 高橋剛士, 太田友樹, 平松直樹, 吾郷由希夫, 松田敏夫
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] 幼若期環境強化によるPACAP 遺伝子欠損マウス学習記憶障害の発現抑制 (2012)
  • Author(s): 中川光, 竹本光佑, 福山留以, 新谷紀人, 橋本均, 吾郷由希夫, 田熊一敞, 松田敏夫
  • Organizer: 生体機能と創薬シンポジウム2012
  • Place of Presentation: 神戸
• [Presentation] 神経型一酸化窒素合成酵素阻害剤7-nitroindazole は6-hydroxydopamine 神経障害ラットにおいてL-DOPA 誘発ジスキネジアの形成を抑制する (2011)
  • Author(s): 太田友樹, 田熊一敞, 高橋剛士, 吾郷由希夫, 松田敏夫
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 石川
• [Presentation] MPTP誘発酸化ストレスおよび中脳ドパミン神経変性にNa^+/Ca^<2+>交感系を介するERK活性化が関与する (2011)
  • Author(s): 梨子田哲明, ら
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] 選択的Na^+/Ca^<2+>交感系阻害薬SEA0400はMPTPによるERK活性化を介した酸化ストレスを抑制しドパミン神経を保護する (2011)
  • Author(s): 太田友樹, ら
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] 選択的Na+/Ca2+交換系阻害はMPTP誘発パーキンソン病マウスモデルの黒質・線条体ドパミン障害を軽減する (2011)
  • Author(s): 田熊一敞, ら
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 石川(招待講演)