Mechanisms mediating metabolic abnormalities in the livers of Ehrlich ascites tumor-bearing mice.
Previously we reported that intermittent intraperitoneal administration of ornithine decarboxylase-inducing factor (ODC factor), interleukin 1alpha (IL-1alpha), and tumor-necrosis factor-alpha (TNF-alpha) to normal mice induced biological changes in the hosts which included changes in the pattern of expression of pyruvate kinase (PK) isozymes in the liver and hypertrophy of the spleen. In the study reported here, we investigated the chronic and combined effects of these factors on hepatic enzymes using alzet microosmotic pumps implanted in the subcutis of the backs or abdominal cavities of mice. Continuous administration of ODC factor and recombinant human IL-1alpha (rhIL-1alpha) reduced the activity of L-type PK, which is a glycolysis-related enzyme in the liver, and induced the activity of M2-type PK, a known marker of liver dedifferentiation. Serine dehydratase (SDH) and tyrosine aminotransferase (TAT), enzymes associated with amino acid metabolism, were not significantly influenced at the examined concentration. The simultaneous continuous infusion of ODC factor and rhIL-1alpha or rhTNF-alpha caused alterations in the patterns of expression of PK isozyme activity profiles and reduced overall PK activity. SDH and TAT activities were also significantly induced. Moreover, mice treated with these combined factors displayed many other metabolic changes normally associated with cancer cachexia. These findings suggest that the tumor-derived ODC factor and cytokines such as IL-1alpha and TNF-alpha might function synergistically in the metabolic perturbations observed in Ehrlich ascites tumor bearers.
Korekane
Hiroaki
H
Department of Biochemistry, Faculty of Science, Okayama University of Science, 1-1, Ridai-cho, Okayama 700-0005, Japan.
Nishikawa
Atsushi
A
Imamura
Kiichi
K
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D012695:L-Serine Dehydratase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011770:Pyruvate Kinase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014444:Tyrosine Transaminase; D011770:Pyruvate Kinase; D009955:Ornithine Decarboxylase; D012695:L-Serine Dehydratase