ODC Activity in the CNS of Vehicle and LPSTreated Mice

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.

Fig. 2. Interrelationship between the polyamine and metabolic pathways of the nitric oxide. See Subheading 2 in text for details.

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