The ODC protein is highly regulated at the levels of transcription and translation, as well as at the posttranslational level. Furthermore, ODC enzyme has a very short halflife. To ascertain that LPS-induced increase in ODC gene expression was really associated with putrescine biosynthesis, ODC activity was measured in control mice and in mice that were treated with a suicide inhibitor of ODC, the difluoromethylornithine (DFMO). ODC activity was strongly induced by sixfold 3 h after a single systemic injection of LPS, which indicates that the latter is able to increase the biosynthesis of putrescine in the brain (61). The enzymatic activity was reduced by 50% in mice that had access to DFMO in their drinking water for 2 d before the systemic LPS challenge. These data demonstrate the ability of DFMO to inhibit the effects of the LPS-induced ODC activity in the brain. Thus the potential that polyamines—or at least putrescine— are overproduced in the brain during endotoxemia exists.
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