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Moderate hypothermia inhibits the death of differentiated PC12 cells mediated by simultaneous exposure to iron and ascorbic acid

Research Project

Project/Area Number 16591082
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionOsaka Medical College

Principal Investigator

OGIHARA Toru  Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 講師 (00211128)

Co-Investigator(Kenkyū-buntansha) SUZUKI Shuhei  Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10278525)
TAMAI Hiroshi  Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (30179874)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHypothermia / Free radical / Hypoxic ischemic encephalopathy / Iron / Ascorbic acid / PC 12 / 新生児仮死
Research Abstract

Hypothermia has attracted much attention as a leading approach for preventing brain damage due to neonatal hypoxic ischemic encephalopathy (HIE), but its appropriate clinical use remains unclear and the theoretical basis is yet to be established. We previously found that non-protein-bound iron and ascorbic acid (AA) levels were increased in the cerebrospinal fluid of HIE infants, and showed that FeSO4 and AA can synergistically induce apoptosis of PC12 cells. In this study, as an in vitro model of hypothermic therapy for HIE, we investigated the effect of hypothermia on Fe-AA cytotoxicity using differentiated PC12 cells. When the cells were exposed to Fe-AA for 48 h, moderate hypothermia (32℃ or 30℃) significantly improved viability (mean values;17.9 % of the unstressed control at 37℃ versus 56.4 % at 32℃ and 77.5 % at 30℃; p < 0.05, respectively). In contrast, mild hypothermia (35℃ or 34℃) had no beneficial effect and severe hypothermia (28℃) exacerbated cell death. A neuroprotective effect was only obvious if hypothermia (32℃) was started within 6 h of exposure. Even if hypothermia was started within 6 h of the insult, at least 24 h of hypothermia was necessary to improve cell viability. Caspase activity was significantly attenuated after 48 h of mild hypothermia. After 48 h of exposure to Fe-AA at 32℃, cell viability was preserved for at least the next 48 h. Taken together, our data were consistent with previous in vivo studies and suggest hypothermic inhibition of Fe-AA cytotoxicity may be one of the underlying mechanisms for cerebral hypothermic therapy.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (10 results)

All 2007 2006 2005 Other

All Journal Article (10 results)

  • [Journal Article] Moderate hypothermia inhibits the death of differentiated PC12 cells mediated by simultaneous exposure to iron and ascorbic acid.2007

    • Author(s)
      Hasegawa M, Ogihara T, Hiroi M, Tamai H
    • Journal Title

      J Neurochem (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia2006

    • Author(s)
      Tohru Ogihara, Kazuya Hirano, Takao Morinobu, Han-Suk Kim, Satoru Ogawa, Mayo Hiroi, Shinya Oue, Ryoichi Ban, Seigo Hira, Masashi Hasegawa, Shigeo Yamaoka, Masako Yasui
    • Journal Title

      Pediatric Research 60

      Pages: 613-618

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia2006

    • Author(s)
      Tohru Ogihara, Kazuya Hirano, Takao Morinobu, Han-Suk Kim, Satoru Ogawa, Mayo Hiroi, Shinya Oue, Ryoichi Ban, Seigo Hira, Masashi Hasegawa, Shigeo Yamaoka, Masako Yasui
    • Journal Title

      Pediat Res. 60

      Pages: 613-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia2006

    • Author(s)
      Tohru Ogihara, Kazuya Hirano, Takao Morinobu, Han-Suk Kim, Satoru Ogawa, Mayo Hiroi, Shinya Oue, Ryoichi Ban, Seigo Hira, Masashi Hasegawa, Shigeo Yamaoka, Masako Yasui
    • Journal Title

      Pediatric research 60

      Pages: 613-618

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia2006

    • Author(s)
      Tohru Ogihara, Kazuya Hirano, Takao Morinobu, Han-Suk Kim, Satoru Ogawa, Mayo Hiroi, Shinya Oue, Ryoichi Ban, Seigo Hira, Masashi Hasegawa, Shigeo Yamaoka, Masako Yasui
    • Journal Title

      Pediatric research (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of apoptosis by glutathione redox state in PC12 cells exposed simultaneously to iron and ascorbic acid.2005

    • Author(s)
      Hiroi M, Ogihara T, Hirano K, Hasegawa M, Morinobu T, Tamai H, Niki E
    • Journal Title

      Free Radical Biology and Medicine 38

      Pages: 1057-1072

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of apoptosis by glutathione redox state in PC12 cells exposed simultaneously to iron and ascorbic acid.2005

    • Author(s)
      Hiroi M, Ogihara T, Hirano K, Hasegawa M, Morinobu T, Tamai H, Niki E.
    • Journal Title

      Free Radic Biol Med. 38

      Pages: 1057-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of apoptosis by glutathione redox state in PC12 Cells exposed simultaneously to iron and ascorbic acid2005

    • Author(s)
      Mayo Hiroi, Tohru Ogihara, Kazuya Hirano, Masashi Hasegawa, Takao Morinobu, Hiroshi Tamai, Etsuo Niki
    • Journal Title

      Free Radical Biology and Medicine 38

      Pages: 1057-1072

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Venepuncture is preferable to heel lance for blood sampling in term neonates2005

    • Author(s)
      Satoru Ogawa, Tohru Ogihara, Emi Fujiwara, Kazumi Ito, Mutsumi Nakano, Satsuki Nakayama, Tomomi Hachiya, Naomi Fujimoto, Hiroko Abe, Satoko Ban, Etsuko Ikeda, Hiroshi Tamai
    • Journal Title

      Archives of Disease in Childhood Fetal Neonatal Edition (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Moderate hypothermia inhibits the death of differentiated PC12 cells mediated by simultaneous exposure to iron and ascorbic acid.

    • Author(s)
      Hasegawa M, Ogihara T, Hiroi M, Tamai H.
    • Journal Title

      J Neurochem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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