Structures, Functions and Medical Meaning of Lysosomal Cysteine Protease Inhibitors
| Project/Area Number |
59065007
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KATUNUMA Nobuhiko School of Medicine, The University of Tokushima, 医学部, 教授 (50035375)
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| Co-Investigator(Kenkyū-buntansha) |
石川 榮治 宮崎医科大学, 教授 (40029939)
KOMINAMI Eiki School of Medicine, The University of Tokushima, 医学部, 講師 (10035496)
ISHIKAWA Eiji Medical College of Miyazaki
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥144,000,000 (Direct Cost: ¥144,000,000)
Fiscal Year 1986: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1985: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1984: ¥126,000,000 (Direct Cost: ¥126,000,000)
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| Keywords | Lysosomes / Cysteine proteinases / Cathepsin / Cystatin / Autophagy / Muscular dystrophy / 細胞内タンパク分解 / オートファジー / 筋ジストロフィー症 / I-cell病 / カテプシン群 / オートリソゾーム / ヘテロリソゾーム / 遠位性ミオパチー |
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| Research Abstract |
We purified lysosomal cysteine proteinases, cathepsins B, H and L and determined the amino acid sequences and carbohydrate structures of cathepsin B and H. Distributions and localizations of three cathepsis in various organs and peripheral blood cells were examined. The content of cathepsin B is extremely high in phagocytes such as macrophages and Kupffer cells and it is induced several fold in inflammatory macrophages. Different localizations of three cathepsins were shown in hepatocytes, pancreatic islet cells and brain. Cystatin <alpha> and <beta> , endogenous cysteine proteinase inhibitors were sequenced and their different tissue distributions were demonstrated. A cysteinyl residue (cys-3) of cystatin- <beta> is involved in regulation of the inhibitory activity by formation of mixed disulfide with glutathione: free form is active and the glutathionated form is inactive. The formation of mixed disulfide of the inhibitor was shown to occur in cultured cells, presumably by the enzymatic reaction. Different regulation of autophagy and heterophagy in liver under various nutritional and hormonal conditions was studied in relating with different localizations of three cathepsins in hepatocytes. Marked accerelation of autophagy and elevation of cathepsins were shown in myofibers of muscle wasting diseases such as distal myopathy with rimmed vacuole and Duchnne type muscle dystrophy, suggesting that the inhibition of cysteine cathepsins in these diseases is expected to supress the progression of muscle atrophy.
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Report
(2 results)
Research Products
(19 results)
