Little is known about the regulation and control of Schistosoma mansoni gene expression. In order to study such mechanisms a gene reporter expression vector construction, under the control of a promoter region derived from the S. mansoni calreticulin gene was used to transfect the human Jurkat T cell line. The promoter region contains potential TATA and CAAT boxes as well as an AP-1 core element. We show here that transcriptional factors of eucaryotic cells may induce a gene reporter activity under the control of a S. mansoni promoter region. Treatment of stably transfected cells with N-acetyl cysteine (NAC), a well-characterized antioxidant which counteracts the effects of reactive oxygen intermediates, enhanced the AP-1 dependent transactivation. This effect was abolished when the SmCaR promoter region was deleted in the AP-1 site. Electrophoretic Mobility Shift Assays showed that the AP-1 sequence of S. mansoni bound to both S. mansoni extracts and in nuclear extracts from Jurkat cells, thus explaining possible activation of AP-1 by NAC. Finally treatment of S. mansoni schistosomula and adult worms with NAC induced an increased synthesis of calreticulin protein suggesting a possible role of redox mechanisms in the regulation of a calreticulin gene transcription process in S. mansoni.

The therapeutic efficacy of mood stabilizers may involve the regulation of gene expression mediated by transcription factor activation. In this study, we investigated AP-1 and cAMP response element-binding protein (CREB) DNA-binding activity in the rat frontal cortex and hippocampus of rats fed a control diet, a lithium diet for 7 wk, or 6 wk of lithium, followed by withdrawal for 7 d. Subsequently, animals were exposed to restraint stress or no stress and the DNA-binding activities assessed at 2, 8 and 24 h post-stress. AP-1 activity was increased in both brain regions by lithium, an effect that persisted with lithium discontinuation. Restraint stress induced AP-1 activity in the frontal cortex of the control group. This stress-induced effect on AP-1 activity was attenuated in lithium-treated and lithium-withdrawn animals. AP-1 DNA binding was also induced by stress in the hippocampus of control animals and the activity diminished over time in the lithium and lithium-withdrawn groups. CREB activity also increased in the frontal cortex and hippocampus of the lithium-treated group. Stress increased CREB activity in the frontal cortex of the controls, and was slightly attenuated with lithium treatment. CREB activity in the hippocampus was insensitive to stress. The proteins involved in the AP-1 and CREB transcription complexes were also characterized. Our findings of increased AP-1 and CREB binding after lithium are consistent with lithium's inhibitory effect on glycogen synthase kinase-3β, which has been show to negatively regulate AP-1 and CREB transcriptional activity.