TRANSCRIPTIONAL REGULATION OF SCHISTOSOMA-MANSONI CALRETICULIN - POSSIBLE ROLE OF AP-1

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 (NAG), 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-I sequence of S. mansoni bound to both S. mansoni extracts and in nuclear extracts from Jurkat cells, thus explaining possible activation of AP-I by NAG. 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.