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Studies for lipid transports in pathogenesis of child diseases

Research Project

Project/Area Number 21591310
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionAkita University

Principal Investigator

TAKAHASHI Tsutomu  秋田大学, 大学院・医学系研究科, 教授 (20270845)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Atsuko  秋田大学, 医学部, 助教 (70400497)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords酸性スフィンゴミエリナーゼ / NPC1 / 新生児虚血性低酸素性脳障害 / 未熟児慢性肺障害 / 細胞内脂質輸送 / リピドーシス / スフィンゴミエリン / コレステロール
Research Abstract

Niemann-Pick disease is a group of disorders characterized by the intracellular accumulation of sphingomyelin and cholesterol, composed of types A/B and type C. Acid sphingomyelinase (ASM) is a lysosomal enzyme to hydrolyze sphingomyelin into ceramide and phsphocholine, deficiency of which causes Niemann-Pick disease type A/B. Recently, ASM has been known as an enzyme to play a critical role in many cellular functions. NPC1, a membrane protein residing in late endosome and lysosome, and NPC2, a lysosomal secretory protein, coordinate in the transport of cholesterol, which enters into lysosome by the LDL receptor pathway, into the cytosol. Mutations in the gene of NPC1 or NPC2 cause Niemann-Pick type C. In our studies, we suggested that ASM play roles in the pathogeneses of ischemic-hypoxic brain damage and chronic lung disease in premature neonate, using 3-year-old rat conditioned with ischemic-hypoxic state and cultured cells of alveolar macrophage from rat. The results suggest the possible therapy through suppression of ASM activation in the diseases of children. In addition, our studies showed that ASM enzyme activity has some effect on the transport of cholesterol via NPC1/NPC2 system in lysosome, suggesting the relation of ASM with intracellular cholesterol metabolism.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (4 results)

All 2011 2010 2009

All Journal Article (4 results) (of which Peer Reviewed: 4 results)

  • [Journal Article] Hypoxia-ischemia induces hypo-phosporyltion of collapsing response mediator rotein 2 in a neonatal rat model of periventricular leukomalacia2011

    • Author(s)
      Sato, Y., Ishida-Nakajima, W., Kawamura, M., Miura, S., Oguma, R., Arai, H., Takahashi, T
    • Journal Title

      Brain Res

      Volume: 1386 Pages: 165-174

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of a new piezoelectric transducer sencer for noninvasive cardiorespiratory monitoring of newborn infants in the NICU2010

    • Author(s)
      Sato, S., Ishida-Najima, W., Ishida, A., Kawamura, M., Miura S., Ono, K., Inagaki, N., Takada, G., Takahashi, T
    • Journal Title

      Neonatology

      Volume: 98 Pages: 179-190

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypical variety of insulin resistance in a family with a novel mutation of the insulin receptor gene2010

    • Author(s)
      Takahashi, I., Yamada, Y., Kadowaki, H., Horikoshi, M., Kadowaki, T., Narita, T., Tsuchida, S., Noguchi, A., Koizumi, A., Takahashi, T
    • Journal Title

      Endocr J

      Volume: 57 Pages: 509-516

    • NAID

      10029585142

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ascorbic acid protects the newborn rat brain from hypoxic-ischemia2009

    • Author(s)
      Miura, S., Ishida, N.W., Ishida, A., Kawamura, M., Ohmura, A., Oguma, R., Sato, Y., Takahashi, T
    • Journal Title

      Brain Dev

      Volume: 31 Pages: 307-317

    • NAID

      10025579596

    • Related Report
      2011 Final Research Report
    • Peer Reviewed

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Published: 2009-04-01   Modified: 2016-04-21  

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