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

• Project/Area Number: 16591082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osaka 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: ¥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)
• Keywords: Hypothermia / 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.

Research Products

• [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
• [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia (2006)
  • 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
• [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia (2006)
  • 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
• [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia (2006)
  • 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
• [Journal Article] Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia (2006)
  • 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)
• [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
• [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
• [Journal Article] Regulation of apoptosis by glutathione redox state in PC12 Cells exposed simultaneously to iron and ascorbic acid (2005)
  • 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
• [Journal Article] Venepuncture is preferable to heel lance for blood sampling in term neonates (2005)
  • 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)
• [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