Induction of Hepatic Key Glycolytic Enzymes by Liver Injury

概要

論文の詳細を見る
Activities of key glycolytic and gluconeogenic enzymes in rat liver were determined following intraperitoneal or intragastric administration of a single dose of 0.1-0.2ml CCl4/100g body weight to male Sprague-Dawley rats under various experimental conditions. Hexokinase (HK), pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G6PDH), and phosphofructokinase (PFK) activities increased significantly in 24 hours, reaching 10, 5, 5 and 2 folds in 72 hours, over respective controls, and returned to the initial values in one week. In contrast with this, glucokinase (GK), glucose 6-phosphatase (G6Pase), and fructose 1, 6-diphosphatase (FDPase) activities decreased significantly, GK activity being undetectable in 48-72 hours. On the other hand, a bifunctional enzyme, aldolase (ALD), showed little change in total activity. The hepatic enzyme pattern in CCl4 liver injury was apparently different from that of fasting and refeeding a glucose-casein mixture. The pattern was similar to that found in undifferentiated cells of regenerating and fetus livers, and of an ascites hepatoma, AH 130. This was supported by the studies of isozyme patterns of some glycolytic enzymes in CCl4-injured rat livers, i. e. loss or decrease of liver specific GK, PK-L, and ALD-B and increase of nonspecific HK-I, II, III, PK-M2, and ALD-A. A single molecular species of G6PDH was involved in increase of its activity under the above experimental conditions of animals. Elevations of HK, PK and G6PDH activities after CCl4 administration were found before the increase in 14C-orotate incorporation into liver DNA became evident. The extent of enhanced DNA synthesis following CC14 liver injury was less than that in liver regeneration after partial hepatectomy. Thioacetamide administration produced a liver enzyme pattern similar to that obtained by CCl4 treatment. However, the mitotic index found in thioacetamide-injured liver was much smaller than in CCl4-injured or hepatectomized liver. Thioacetamide caused also less liver cell necrosis and fatty change. These results apparently indicate that the increase in liver glycolytic enzyme activities in CCl4 intoxication is not a reflection of liver regeneration following hepatic cell necrosis, in terms of DNA synthesis and cell division, and has no relevance to liver cell necrosis and fatty change per se. Parabiosis experiments partially excluded involvement of a humoral factor in increasing the glycolytic enzyme activities following CCl4 treatment. Thus, it appears most likely that the enhanced enzyme activities in CCl4 intoxication represent a positive response of parenchymal liver cells to the injury, this being directed to survival and repair of the damaged hepatic cells. Cycloheximide administration suppressed the increases in HK, PK and G6PDH activities in CC14-injured liver, suggesting that the increase in enzyme activity is due to enzyme induction. On the other hand, actinomycin D treatment twice a day in a single dose of 50μg/100g body weight failed to suppress the increase in enzyme activity. The dietary induction of G6PDH was impaired, even though G6PDH could be induced by thioacetamide intoxication, indicating the difference existing between these two induction mechanisms. Pathophysiological significances of the enzyme induction by liver injury were discussed.
Japan Society of Clinical Chemistryの論文

Induction of Hepatic Key Glycolytic Enzymes by Liver Injury

スポンサーリンク

概要

著者

関連論文

スポンサーリンク