| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1985: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1984: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1983: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Research Abstract |
1. Administration of Ep459-asialofetuin conjugate (Ep459-AF) and pepstatinasialofetuin conjugate (Ps-AF) to rats effectively inhibited lysosomal thiol proteinases and cathepsin D in the liver, respectively, at a very low dose. Ep 459-AF treatment also led to an accumulation of autolysosomes in rat liver. There was a close correlation between the accumulation of autolysosomes and the inhibition of thiol proteinases. However, as opposed to the inhibition of thiol proteinases, the inhibition of cathepsin D did not cause accumulation of autolysosomes in the rat liver. These results suggest that autophagy in rat hepatocytes is a common occurrence under normal physiological conditions and that thiol proteinases are digestive enzymes essential for the autolysis.
2. After administration of Ps-AF or Ep459-AF, intracellular protein degradation of isolated rat liver parenchymal cells. is inhibited about 20 % by Ps-AF and 55 % by Ep459-AF, respectively. When both drugs were administered simultaneously, inhibition of protein degradation increased additively, and reached about 66 %. In this case, serious cell injury was observed by electron microscopy. An increase in blood GOT value was observed obviously 6 h after administration, and this value reached maximum after 24 h and then decreased rapidly.
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