| Japanese |
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| Title | グリコーゲン脱分枝酵素阻害薬N-methyl-1-deoxynojirimycinによる虚血心筋保護のメカニズム |
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| Subtitle | 特集 第20回日本循環制御医学会総会 若手研究者発表コンペティション |
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| Authors | 荒井正純, 湊口信也, 熊田裕一, 宇野嘉弘, 西田佳雄, 王寧元, 橋本和明, 藤原久義 |
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| Organization | 岐阜大学医学部第2内科 |
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| Journal | 循環制御 |
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| Volume | 21 |
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| Number | 1 |
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| Page | 5-9 |
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| Year/Month | 2000/ |
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| Article | 報告 |
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| Publisher | 日本循環制御医学会 |
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| Abstract | 「要旨」 α-1, 6-glucosidase阻害薬であるN-methyl-1-deoxynojirimycin(MOR-14)は, 虚血中の嫌気性糖代謝を抑制し心筋梗塞サイズをischemic preconditioningと同程度に減少させる. 本研究において著者らは, MOR-14の心筋保護のメカニズムを詳細に検討するため, ischemic preconditioningにおける主要なmediatorであるprotein kinase C(PKC)の関与について検討した. ウサギを, control群(n=10), MOR-14を虚血10分前に投与したMOR-14群(n=10), PKCのblockerであるstaurosporineをMOR-14の10分前に投与したstaurosporine+MOR-14群(n=10)に分け, 冠動脈を30分結紮-48時間再灌流した後TTC染色で梗塞を定量した. |
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| Practice | 基礎医学・関連科学 |
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| Keywords | N-methyl-1-deoxynojirimycin, Protein kinase C, Anaerobic glycolysis, Preconditioning |
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| English |
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| Title | Mechanisms of Cardioprotection Afforded by N-Methyl-1-Deoxynojirimycin, an α-1, 6-Glucosidase Inhibitor:Involvement of Protein Kinase C |
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| Authors | Masazumi Arai, Shinya Minatoguchi, Hirokazu Kumada, Yoshihiro Uno, Yoshio Nishida, Ningyuan Wang, Kazuaki Hashimoto, Hisayoshi Fujiwara |
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| Organization | The Second Department of Internal Medicine,Gifu,Japan |
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| Journal | Circulation Control |
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| Volume | 21 |
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| Number | 1 |
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| Page | 5-9 |
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| Year/Month | 2000/ |
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| Article | Report |
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| Publisher | Japan Society of Circulation Control |
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| Abstract | We previously demonstrated that preischemic treatment with N-methyl-1-deoxynojirimycin (MOR-14) attenuates anaerobic glycolysis by inhibiting α-1, 6-glucosidase activity of glycogen debranching enzyme and markedly reduces infarct size. However, it is unknown whether the beneficial effect is due to direct protection against cytotoxicity of accumulated products of anaerobic glycolysis. To further clarify the precise mechanism, we investigated whether the cardioprotective effect is dependent on protein kinase C (PKC), a main mediator of ischemic preconditioning. Rabbits were subjected to 30 min ischemia followed by 48 hrs reperfusion. The infarct sizelimiting effect of MOR-14 was completely blunted when 50μg/kg of staurosporine, a PKC inhibitor, was administered 10 min prior to MOR-14 injection although staurosporine alone did not alter the infarct size. However, after 30 min of ischemia, glycogen and lactate levels in the staurosporine + MOR-14 group were similar to those in MOR-14 alone group and significantly different from those in the control group. Immunoblot analysis of PKC- was performed using Langendorff-perfused rabbit hearts. Ischemia caused translocation of PKC-ε from the cytosol to the membrane fraction, peaking at 20 min of ischemia. At 20 and 30 min of ischemia, the amount of PKC-ε in the membrane fraction were significantly more than those in the control group. These data suggest that PKC, rather than glycogenolytic inhibition, is the main mechanism of cardioprotection afforded by MOR-14. |
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| Practice | Basic medicine |
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| Keywords | N-methyl-1-deoxynojirimycin, Protein kinase C, Anaerobic glycolysis, Preconditioning |
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