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Neuron dysfunction in bilirubin-induced apoptosis causes kernicterus

Research Project

Project/Area Number 10671018
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionTokyo Medical and Dental University, Medical Research Institute

Principal Investigator

YAMAGUCHI Tokio  Tokyo Med. & Dent. Univ., Medical. Res. Inst., Associate Prof., 難治疾患研究所, 助教授 (30134745)

Co-Investigator(Kenkyū-buntansha) ASAKA Rei  Tokyo Med. & Dent. Univ., Medical. Res. Inst., Res. Assistant, 難治疾患研究所, 助手 (20167224)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsbilirubin / kernicterus / apoptosis / neuron / biliverdin / urobilin / stercobilin / mitochondria
Research Abstract

Neonatal jaundice continues to acommon problem. Kernicterus, although rare, continues to be a very real concern in both full-time and preterm infants. This neurologic syndrome has been associated with selective neuronal vulnerability in the basal ganglia, certain brainstem nuclei, and Purkinje cells. However, the mechanism by which bilirubin damages neurons remains unclear. In these studies, we found that bilirubin caused kernicterus in bilirubin-induced apoptosis. In primary cultured neuron, bilirubin (30μg/ml) completely damaged neuron (CGC : Cerebral Granular Cells) by the mechanism of apoptosis style, but not necrosis style in the DMEM containing 10% calf serum albmin. To ours surprise, biliverdin in spite of the low concentration (3μg/ml) did not change the viability of neurons (CGC). On the other side, urobilin and stercobilin did not show the toxicity regardless of the low concentration (30μg/ml) at all. However, if there are in both bilrubin and CaィイD12+ィエD1ion (CaSOィイD24ィエD2), neurons did not undergone apoptosis. Secondly, we have examined the distribution of bilirubin in intracellular neuron. Interestingly, bilirubin was localized in mitochondria among intracellular organelle of neurons.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Shinobu Hayashi et al.: "Induction of Reme oxygenase-I suppresses venular leukocyteadhesion elicited byoxidative stress"Circulation Research. 85. 663-671 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuichi Shinoda et al.: "Carbon monoxide as a regulator of bile canalicular in cultured rat hepato cytes"Hepatology. 28(2). 286-296 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokio Yamaguchi et al.: "Bilirubin oxidation provoked by treatment is suppressed by feeding ascorbic acid in a mutant unabled to synthesize ascorbic acid"Eur. J. Biochem.. 245. 233-240 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuyoshi Sano et al.: "Endogenecus carbon monoxide suppression stimulates bile acid-deperdent biliary transport in perfused rat liver"Am. J. Physiol.. 272. G1268-G1275 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tadashi Sakai et al.: "Severe oxidative stress is throught to be a principal cause of jaundice of yellowtail Serina Quinqeradista"Aquaculture. 160. 205-214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokio Yamaguchi et al.: "Taulo cholate induces directional excretion of bilirukin into bile in the perfusedl rat liver"Am. J. Physiol.. 270. G1028-G1032 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 山口登喜夫他: "日本臨床(第750号増刊) 広範囲 血液・尿化学検査〜その数値をどう読むか〜"日本臨床社. 824(327-332) (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 山口登喜夫他: "Free Radicals in Clinical Medicines Vol. II) フリーラジカルの臨床"日本医学館 (監修 : 近藤元治). 119(79-84) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, S., Takamiya, R., Yamaguchi, T., et al.: "Induction of heme ovygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress : Role of bilirubin generated by the enzyme."Circ. Res.. 85. 663-671 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinoda, Y., Suematatsu, M., Wakabayashi, Y., Goda, N., Suzuki, t., Saito, T., Yamaguchi, T., et al.: "Carbon monoxide as a regulator of bile canalicular in cultured rat hepatocytes."Hepatology. 28(2). 286-296 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi, T., Hashizume, T., Tanaka, M., Nakayama, M., Sugimoto, A., Ikeda, S., Nakajima, H., and Horio, F.: "Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid."Eur. J. Biochem.. 245. 233-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sano, T., Shimomi, M., Wakabayashi, Y., Shinoda, Y., Goda, N., Yamaguchi, T., Nimura, Y., Ishimura, Y., and Suematsu, M.: "Endogeneous carbon monoxide suppression stimulates bile acid-dependent biliary transport in perfused rat liver."Am. J. Physiol.. G1268-G1275 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi, T., M. Terakado, F. Horio, K. Aoki, M. Tanaka, and H. Nakajima: "Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase."Biochem. Biophys. Res. commun.. 223. 129-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi, T., Y. Wakabayashi, M. Tanaka, T. Sano, H. Ishikawa, H. Nakajima, M. Suematsu, et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver."Am. J. Physiol.. 270. G1028-G1032 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sinobu Hayashi et al.: "Induction of heme oxygenase-1 suppresses venulor laukocyte adhesion elicited by oxidative stress."Circulation Research. 85. 663-671 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuichi Shinoda et al.: "Carbon monoxide as a regulator of bile conalicular in cultured rat Nepatocytes."Hepatology. 28(2). 286-296 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Bilirubin oxidation provoked by treatment is suppressed by feeding ascorbic acid in a mutant unabled tosynthesize ascorbic acid"Eur. J. Biochem.. 245. 233-240 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuyoshi Sano et al.: "Endogeneous carbon monoxide suppression stimulates bile acid dependent biliary transport in perfused rat liver."Am. J. Physiol.. 272. G1268-G1275 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tadashi Sakai et al.: "Severe oxidative stress is thought to be a principal cause of jaundice of yellowtail Serina Quingeradiata."Aguacu Hare. 160. 205-214 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfused rat liver."Am. J. Physiol.. 270. G1028-G1032 (1996)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山口登喜夫 他: "日本臨床(第750号増刊)広範囲血液・尿化学検査・免疫学的検査 -その数値をどう読むか-"日本臨床社. 824(327-332) (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 山口登喜夫 他: "Free Rachicels in Clinical Medicine (フリーラジカルの臨床 Vol 11)"日本医学館(監修:近藤元治). 119(79-84) (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokio Yamaguchi, et al.: "Bilirubin oxidation grovoked by treatrnent is suppressed by feeding ascorbic acid in a mutant urable to synthesize ascorbic acid" Eur. J. Biochem.245. 233-240 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuichi Shinoda et al.: "Carbon monoxide as a regulator of bike canalicular in cultured not hepatooytes" Hepatology. 28(2). 286-296 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuyoshi Sano et al.: "Endogeneous carbon monoxide suppression stimulates bile acid-deperdent biliary transport in perfused rat liver" Am. J. Physid.272. G1268-G1275 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tadashi Sakai et al.: "Severe oxidative stress is thoaght to be a principal cause of jaurdice of yellow tail Seriola Quiageradiata" Aquaculture. 160. 205-214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tokio Yamaguchi et al.: "Taurocholate induces directional excretion of bilirubin into biles in the perfuced rat liver." Am. J. Physiol.270. G1028-G1032 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tokio Yamaguchi: "Role of bilirubin as an anti-oxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenace" Biochem. Biophys. Res. Commun.223. 129-135 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山口登喜夫 他: "Free Radicals in Clinical Medicine. フリーラジカルの臨床Tol11" 日本医学館(監修 : 近藤元治), 119 担当79-84 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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