Induction of MnSOD gene expression in a hepatic model of TNF-alpha toxicity does not result in increased protein
| Autor: | Mark J. Czaja, A. Compton, L. W. Oberley, M. L. Schilsky, Yang Xu, L. Ridnour, P. Schmiedeberg |
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| Rok vydání: | 1994 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Lipopolysaccharide Physiology animal diseases Gene Expression Galactosamine Biology Superoxide dismutase Rats Sprague-Dawley chemistry.chemical_compound Downregulation and upregulation Physiology (medical) Internal medicine Gene expression medicine Animals RNA Messenger Uridine Liver injury Hepatology Superoxide Dismutase Tumor Necrosis Factor-alpha fungi Gastroenterology Hepatotoxin medicine.disease Rats enzymes and coenzymes (carbohydrates) Endocrinology chemistry Liver Toxicity biology.protein Tumor necrosis factor alpha |
| Zdroj: | The American journal of physiology. 266(4 Pt 1) |
| ISSN: | 0002-9513 |
| Popis: | The model of toxic liver injury was used to examine the role of manganese superoxide dismutase (MnSOD) expression in cellular resistance to tumor necrosis factor (TNF)-alpha toxicity. The effects of the hepatotoxin D-galactosamine (GalN) and lipopolysaccharide (LPS) on hepatic and splenic TNF-alpha and MnSOD expression were studied. Treatment with GalN and LPS alone or in combination led to equivalent increases in hepatic and splenic TNF-alpha gene expression. Hepatic MnSOD mRNA levels were not affected by GalN or GalN with LPS but were increased 13-fold by LPS alone. Splenic MnSOD mRNA levels were increased twofold by GalN and 12-fold by either LPS alone or GalN plus LPS. The determination of MnSOD protein content, however, revealed no changes in hepatic or splenic steady-state levels of the protein with any of the treatments, despite the marked increases in MnSOD gene expression. Hepatic MnSOD enzyme activity was also unchanged by LPS or GalN plus LPS administration. Biosynthesis of MnSOD protein in rat hepatocytes isolated from an in vivo LPS-treated rat was unchanged compared with control. MnSOD mRNA levels were increased when GalN treatment was combined with uridine rescue, but again no change in protein was seen. The lack of any increase in MnSOD protein after GalN or LPS administration indicates that MnSOD upregulation is not involved in cellular resistance against TNF-alpha cytotoxicity in the liver in vivo. |
| Databáze: | OpenAIRE |
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