| Project/Area Number |
02454159
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
KOMINAMI Eiki Juntendo University School of Medicine Professor, 医学部, 教授 (10035496)
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| Co-Investigator(Kenkyū-buntansha) |
KATUNUMA Nobuhiko Tokushima University, Institute for Enzyme Research, Professor, 酵素科学研究センター, 教授 (50035375)
ISHIDOH Kazumi Juntendo University School of Medicine, Assistant, 医学部, 助手 (40212906)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1990: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | Lysosomes / Proteinase / Cathepsin / Bone resorption / Neuron / Degeneration / Alzhieimer's disease |
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| Research Abstract |
Osteoporotic rats prepared by feeding of ca^<2+>-deficient diet showed an elevation of cathepsin B and L activities in femur with the osteoporosis. Administration of E-64 caused marked decreases in the activities of cathepsins in the femur and in the blood ca^<2+>level. But specific inhibition of cathepsin B in the femur in vivo caused no decrease of ca^<2+>level in the blood. We have observed that much larger amount of cathepsin L than cathepsin B is secreted into medium from cultured bone by the addition of PTH or vitamin D3. Exclusive localization of cathepsin L in osteoclasts was shown. From those results cathepsin L might play a most important role on decalcification by degradation of bone matrix proteins.
Immunoreativities of lysosomal cysteine proteinases in the CAl region of the hypocampus of gerbil following transient ischemia showed marked changes in neurons and glial cells. Cathepsins B and L present in normal neurons showed variable immunoreactivities, depending on degeneration of cells. Cathepsin H that was not detectable in neurons appeared within 12 hours in glia cells(passively microglia)in the CAI region. Proliferation of astrocytes around CAI region became prominent after 7th day. In Alzheimer brain cathepsins and other acid hydrolases in neurons were present both in lysosomes of degenerative cells and in senile plaques. Those abnormal extracellular localization of cathepsins and dysregulation can account for multiple hydrolytic events in B amyloid formation.
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