Role of protein kinase C in the reduction of infarct size by N-methyl-1-deoxynojirimycin, an α-1,6-glucosidase inhibitor
| Autor: | Arai, Masazumi, Minatoguchi, Shinya, Kumada, Hirokazu, Uno, Yoshihiro, Nishida, Yoshio, Hashimoto, Kazuaki, Wang, Ningyuan, Takemura, Genzou, Fujiwara, Takako, Higashioka, Masaya, Kuwano, Keiichi, Fujiwara, Hisayoshi |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
1-Deoxynojirimycin Time Factors Myocardium Myocardial Infarction Biological Transport alpha-Glucosidases Isoenzymes nervous system Papers polycyclic compounds Lactates Animals Glycoside Hydrolase Inhibitors cardiovascular diseases Rabbits Enzyme Inhibitors human activities Glycogen Protein Kinase C |
| Popis: | Preischaemic treatment with N-methyl-1-deoxynojirimycin (MOR-14), an alpha-1,6-glucosidase inhibitor, attenuates glycogenolysis and lactate accumulation during ischaemia and markedly reduces infarct size in rabbit hearts. In the present study, we have investigated whether protein kinase C (PKC), a principal mediator of ischaemic preconditioning, is also involved in the cardioprotective effect of MOR-14. To assess the effect of PKC inhibition on infarct size in MOR-14-treated hearts, 38 rabbits were subjected to 30 min of ischaemia followed by 48 h of reperfusion. Infarct size, as a per cent of area at risk, was significantly smaller in rabbits administered 100 mg kg(-1) of MOR-14 10 min before ischaemia (17+/-2%, n=10), than in a control group (46+/-5%, n=10). This beneficial effect of MOR-14 was abolished when 5 mg kg(-1) of chelerythrine, a PKC inhibitor, was given 10 min prior to MOR-14 injection (39+/-4%, n=10), although chelerythrine alone did not alter infarct size (43+/-4%, n=8). Further, chelerythrine had no effect on MOR-14-induced attenuation of glycogen breakdown and lactate accumulation in hearts excised at 30 min of ischaemia. Immunoblot analysis of PKC in homogenates of Langendorff-perfused rabbit hearts revealed that MOR-14 significantly increased levels of PKC-epsilon in the particulate fraction at 20 and 30 min of ischaemia and in the cytosolic fraction at 30 min of ischaemia. Taken as a whole, our data suggest that PKC acts downstream of the inhibition of glycogenolysis by MOR-14 to reduce infarct size. Thus, activation of PKC is a more direct mediator of the cardioprotection afforded by MOR-14 than is inhibition of glycogenolysis. |
| Databáze: | OpenAIRE |
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