Manganese superoxide dismutase: a hepatic acute phase protein regulated by interleukin-6 and glucocorticoids

The superoxide dismutases (SODs) are important metallo-enzymes which scavenge and dismutate the superoxide free radical. They are thought to be the main enzymes in the antioxidant defense system. Identification of stimuli that control transcription of the SOD genes is essential for understanding SOD...

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Bibliographic Details
Published inEndocrinology (Philadelphia) Vol. 129; no. 5; p. 2376
Main Authors Dougall, W C, Nick, H S
Format Journal Article
LanguageEnglish
Published United States 01.11.1991
Subjects
Acute-Phase Proteins - metabolism
Animals
Cycloheximide - pharmacology
Cytokines - physiology
Dactinomycin - pharmacology
Endotoxins - pharmacology
Glucocorticoids - physiology
Interleukin-6 - physiology
Liver - cytology
Liver - metabolism
RNA, Messenger - metabolism
Salmonella typhimurium
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
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Summary:The superoxide dismutases (SODs) are important metallo-enzymes which scavenge and dismutate the superoxide free radical. They are thought to be the main enzymes in the antioxidant defense system. Identification of stimuli that control transcription of the SOD genes is essential for understanding SOD gene regulation. In this study we show that manganese SOD (MnSOD) mRNA levels are elevated by lipopolysaccharide, a bacterial endotoxin, in rat liver. However, neither lipopolysaccharide nor tumor necrosis factor-alpha had an effect on MnSOD mRNA expression in cultured primary hepatocytes. On the other hand, the inflammatory cytokines, interleukin-1 (IL-1) and IL-6 did increase MnSOD mRNA levels, either 2- or 15-fold, respectively, over a 20-h period in hepatocytes. The IL-6-induced increase in MnSOD mRNA levels was attenuated by dexamethasone, a glucocorticoid, in hepatocytes cultured for less than 16 h. In contrast, in hepatocytes originally cultured for more than 16 h, IL-6 and dexamethasone produced a synergistic increase in MnSOD mRNA levels. The induction of MnSOD expression by IL-6, which is a known inflammatory cytokine, suggests that MnSOD may play a role in the inflammation process. Since inflammation is known to result in oxidative damage to cells, the role of MnSOD may be to protect cells from inflammation-mediated oxidative damage.
ISSN:0013-7227
DOI:10.1210/endo-129-5-2376