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Prevention of apoptosis by p21 gene tranfer in central nervous system

Research Project

Project/Area Number 09470300
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNagoya City University

Principal Investigator

YAMADA Kazuo  Nagoya City University, Neurosurgery, Professor, 医学部, 教授 (90150341)

Co-Investigator(Kenkyū-buntansha) IWATA Akira  Nagoya City University, Neurosurgery, Lecturer, 医学部, 助手 (90275131)
AIHARA Noritaka  Nagoya City University, Neurosurgery, Lecturer, 医学部, 助手 (00264739)
NAKANISHI Makoto  Nagoya City University, Biochemistry, Associate Professor, 医学部, 助教授 (40217774)
KATO Taiji  Nagoya City University, Neurosurgery, Professor, 医学部, 教授 (60094364)
MASAGO Atsuo  Nagoya City University, Neurosurgery, Lecturer, 医学部, 助手 (70209419)
FUSE Takahisa  Nagoya City University, Neurosurgery, Assitant Professor (00229080)
KOMATSU Hiroaki  Nagoya City University, Neurosurgery, Lecturer (90305540)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordsp21 / mild cerebral ischemia / apoptosis / immediate early gene / stress gene / glia / forced p21 expression / P21強制発現 / p21 / p21強制発現 / 細胞周期
Research Abstract

We have detected p21 mRNA expression in various types of brain injury models, which includes focal cerebral ischemia, neurotrauma and subarachnoid hemorrhage. The p21 mRNA expression was compared to the other gene expression such as heat shock protein (hsp)-70, c-fos and c-jun. In the focal ischemia, p21 expression was detected in the area of ischemia and penumbra zone with maximal expression at 12-24 hours after ischemi. Hippocampal pyramidal cells of the ischemia side also showed p21 mRNA expression. The p21 mRNA expression has time delay as compared to expression of c-fos, c-jun and hsp-70, indicating different intracellular signalling pathway. Neurons showed more p21 mRNA expression than glia. Western blot study confirmed p21 protein expression in the ischemic hemisphere. Similar results were obtained in the neurotrauma model indicating p21 response as an ubiquitous response of neurons against injury. We detected p21 mRNA expression in the subarachnoid hemorrhage model which caused apoptosis due to mild ischemia in the pefforated side hippocampus. The peak expression in subarachnoid hemorrhage lasted from 24 hours till 120 hours. Neuronal apoptosis in this model occurred within 48 hours. These data suggest that p21 did not cause apoptosis but act as cell recovery from stress. We then detected regurating substance for p21 gene expression in the glioma cell line. In this study, p21 mRNA were upregulated with prostanoids indicating possible cell cycle-regulating drugs.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] Tanikawa M, Yamada K, et al: "Potent prostaglandin A1 analogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E" J Biol Chem. 273. 18522-18527 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Katano H, Yamada Yamada K, et al: "Differential induction of immediate early gene mRNAs following cryogenic and impact trauma with/without craniotomy in rats" Brain Res. 800. 69-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fuse T, Yamada K, et al: "Heat-induced apoptosis in human glioblastoma cell line A172" Neurosurgery. 42. 843-849 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harada S, Yamada K, et al: "Subarachnoid hemorrhage induces c-fos, c-jun and hsp70 mRNA expression in rat brain" Neuroreport. 8. 3399-3404 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Katano H, Yamada K, et al: "Marked alteration of c-fos and c-jun but not hsp70 messenger RNA expression in rat brain after cold-induced trauma : An in situ hybridization study" Restr Neurol Neurosci. 11. 153-160 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwata A, Yamada K, et al: "Expression of basic fibroblast growth factor mRNA after transient focal ischemia : Comparison with expression of c-fos, c-jun, and hsp70 mRNA" J Neurotrauma. 14. 201-210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada K, et al: "Ito U et al (eds), Maturation Phenomenon in Cerebral Ischemia II" Springer-Verlag, Berlin Heidelberg, 27-32 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 山田和雄: "神経栄養因子 山口武典、内山真一郎、松本昌泰、峰松一夫、高木 誠(編)脳卒中学The frontiers of Storokology" 医学書院, 261-270 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanikawa M, Yamada K, Tominaga K, Morisaki H, Kaneko Y, Ikeda K, Suzuki M, Kiho T, Tomokiyo K, Furuta K, Noyori R, Nakanishi M: "Potent prostaglandin A1 sanalogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E" J Biol Chem. 273. 18522-18527 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Katano H, Masago A, Harada S, Iwata A, Yamada k: "Differential induction of immediate early gene mRNAs following cryogenic and impact trauma with/without craniotomy in rats" Brain Res. 800. 69-77 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto T, Masago A, Yamada K, Iwata A, Harada S, Mase M: "Expression of immediate early gene c-fos in rat brain following increased intracranial pressure" Acta Neirochir. 71. 195-199 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fuse T, Yoon K-W, Kato T, Yamada K: "Heat-induced apoptosis in human glioblastoma cell line A172" Neurosurgery. 42. 843-849 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto T, Nakatsuka M, Yamada K, Masago A, Mase M: "Damage of the dentate gyrus in hydrocephalic rat ; changes of hsp, bax, bc1-2 mRNA" Adv Neurotrauma Res. 9. 13-17 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harada S, Kamiya K, Masago A, Iwata A, Yamada K: "Subarachnoid hemorrhage induces c-fos, c-jun and hsp70 mRNA expression in rat brain" Neuroport. 8. 3399-3404 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Katano H, Masago A, Yamada K: "Marked alteration of c-fos and c-jun but not hsp70 messenger RNA expression in rat brain after cold-induced trauma : An in situ hybridization study" Restr Neurol Neurosci. 11. 153-160 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwata A, Masago A, Yamada K: "Expression of basic fibroblast growth factor mRNA after transient focal ischemia : Comparison with expression of c-fos, c-jun, and hsp70 mRNA" J Neurotrauma. 14. 201-210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanikawa M,Yamada K,et al: "Potent prostaglandin A1 analogs that suppress tumor cell growth through induction of p21 and reduction of cyclin E" J Biol Chem. 273. 18522-18527 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katano H,Yamada Yamada K,et al: "Differential induction of immediate early gene mRNAs following cryogenic and impact trauma with/without craniotomy in rats" Brain Res. 800. 69-77 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fuse T,Yamada K,et al: "Heat-induced apoptosis in human glioblastoma cell line A172" Neurosurgery. 42. 843-849 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Harada S,Yamada K,et al: "Subarachnoid hemorrhage induces c-fos, c-jun and hsp 70 mRNA expression in rat brain" Neuroreport. 8. 3399-3404 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katano H,Yamada K,et al: "Marked alteration of c-fos and c-jun but not hsp 70 messenger RNA expression in rat brain after cold-induced trauma : An in situ hybridization study" Restr Neurol Neurosci. 11. 153-160 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwata A,Yamada K,et al: "Expression of basic fibroblast growth factor mRNA after transient focal ischemia : Comparison with expression of c-fos, c-jun, and hsp70 mRNA" J Neurotrauma. 14. 201-210 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada K,et al: "Ito U et al(eds), Maturation Phenomenon in Cerebral Ischemia II" Springer-Verlag, Berlin Heidelberg, 27-32 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山田和雄: "神経栄養因子.山口武典、内山真一郎、松本昌泰、峰松一夫、高木誠(編)脳卒中学The frontiers of Storokology" 医学書院, 261-270 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuguchi T, Kohmura E,: "Expression of tPA mRNA in the facial nucleus following facial nerve transection in the rat." Neuro Report. 8. 419-422 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwata A, Masago A,: "Expression of basic fibroblast growth factor mRNA after transient focal ischemia:Comparison with expression of c-fos,c-jun,and hsp 70 mRNA." J Neurotrauma. 14. 201-210 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuguchi T, Kohmura E,: "Expression of growth inhibitory factor mRNA after focal ischemia in rat brain." J Cered Bloob Flow Metab. 17. 745-752 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katano H, Masago A,: "Marked alteration of c-fos and c-jun but not hsp 70 messenger RNA expression in rat brain after cold-induced trauma:An in situ hybridization study." Restr Neurol Neurosci. 11. 153-160 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Umemura A, Yamada K,: "Production of platelet-activating factor during focal cerebral ischemia and reperfusion in the rat." J Stroke Cerebrovasc Dis. 6. 394-397 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Harada S, Kamiya K,: "Subarachnoid hamorrhage induces c-fos,c-jun and hsp 70 mRNA expression in rat brain." Neuro Report. 8. 3399-3404 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fuse T, Yamada K,: "Heat shock-madiated cell cycle arrest is accompanied by induction of p21 CKI." Biochem Biophys Res Commun. 225. 759-763 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masago A, Shimada S,: "GLAST mRNA expression in the periventricular area of experimental hydrocephalus." Neuro Report. 7. 2565-2570 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Umemura A, Yamada K:"Contribution of cerebrovascular parasympathetic and sensory innervation to the development of cerbral edema in rat focal ischemia and reperfusion." Neurosci Lett. 215. 134-136 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katano H, Masago A,: "Expression of immediate early genes and heat shock protein mRNA following cryogenic brain injury in rats." Adv Neurotrauma Res. 8. 31-33 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mase M, Yamada K,: "CSF flow velocity in aqueduct and intracranial compliance in Normal pressure hydrocephalus after subarachnoid hemorrhage." Curreut Tr Hyd (ToKyo). 6. 42-47 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 布施孝久、山田和雄: "温熱刺激によるグリオーマ細胞周期の変化とp21Cdkインヒビターの発現." 神経化学. 35. 424-425 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄、布施孝久:"神経細胞のアポトーシス" ファルマシア. 33. 356-359 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 原田重徳、神谷 健、: "ラットくも膜下出血(SAH)後早期の脳内遺伝子発現-血管攣縮による症状発現との関連性-" 脳血管攣縮. 12. 229-233 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 金井秀樹、真砂敦夫、: "虚血性神経細胞障害におけるカルパインの作用." Brain Hypoxia. 11. 29-34 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 神谷 健、山田和雄:"クモ膜下出血." 総合臨床. 46. 109-113 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松本勝美、山田和雄:"脳虚血におけるアデノシンの役割と脳虚血治療への応用." 循環器科. 41. 16-22 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsumoto K, Sakaki T,: "Amelioration of ischemic brain damage by the preischemic administration of propentofylline (HWA285) in a rat focal ischemia." Brain Res. 723. 228-230 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄、真砂敦夫、: "成長因子と神経可塑性up-to-date." ブレインサイエンス. 7. 141-147 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄、真砂敦夫、: "脳虚血と神経栄養因子." 現代医療. 28. 1227-1232 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄: "神経栄養因子の遺伝子発現と受容機構." Jpn J Neurosurg. 5. 118-127 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄、真砂敦夫:"虚血と神経栄養因子." 脳と循環. 1. 260-265 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 真砂敦夫、山田和雄、: "ラット中大脳動脈閉塞モデルにおける海馬特異的セリンプロテアーゼ(neuropsin) mRNAの発現変化について." 神経化学. 35. 308-309 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 真砂敦夫、山田和雄、: "水頭症性脳浮腫における上衣下細胞群のグルタメートランスポーター(GLAST)遺伝子の発現." 第18回脳浮腫研究会報告書. 65-74 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamada K, Masago A,: "Maturation Phenomenon in Cerebral Ischemia II. Springer-Verlag," Ito U, Kirino T, Kuroiwa T, Klatzo I (eds),6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山田和雄、中塚雅雄、: "脳機能の解明-21世紀に向けて-九州大学出版会" 赤池紀扶、東 英穂 他(編集), 7 (1998)

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  • [Publications] 山田和雄: "最新脳神経外科学、坪川孝志、高倉公朋、菊池晴彦(編集)" 朝倉書店、, 13 (1996)

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  • [Publications] 杉野文彦、山田和雄:"Microsurgeryの支援システムにおける脳槽の形態評価.佐藤 修(鑑修) Neuroendoscopic Surgery、神経内視鏡の基礎知識と手術手技" 三輪書店、, 10 (1996)

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  • [Publications] 松本 隆、真砂敦夫、: "髄膜をめぐる諸問題 山嶋哲盛、木田真也(編集)" サイメッド・パブリケーションズ、, 9 (1997)

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  • [Publications] 山田和雄、神谷 健: "脳神経外科レビュー3、佐藤 潔、福井仁士、山浦 晶(編集)" 三輪書店、, 9 (1995)

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Published: 1997-04-01   Modified: 2016-04-21  

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