Induction of Schistosoma mansoni Glutathione S-Transferase by Xenobiotics

VandeWaa, Elizabeth A.; Campbell, Carla K.; O’Leary, Kathleen A.; Tracy, James W.

doi:10.1006/abbi.1993.1249

Cited by 17 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteins encoded by these genes are likely involved in fertilization or egg production in the female parasite. Studies on S. mansoni has reported functions of P450 and GST in the parasite [26]. However, this is the first report which reveals more complete connection of the enzymes in the xenobiotic metabolism pathway in S. japonicum .…”

Section: Discussionmentioning

confidence: 74%

Global Expression Analysis Revealed Novel Gender-Specific Gene Expression Features in the Blood Fluke Parasite Schistosoma japonicum

et al. 2011

View full text Add to dashboard Cite

Background Schistosoma japonicum is one of the remarkable Platyhelminths that are endemic in China and Southeast Asian countries. The parasite is dioecious and can reside inside the host for many years. Rapid reproduction by producing large number of eggs and count-react host anti-parasite responses are the strategies that benefit long term survival of the parasite. Praziquantel is currently the only drug that is effective against the worms. Development of novel antiparasite reagents and immune-prevention measures rely on the deciphering of parasite biology. The decoding of the genomic sequence of the parasite has made it possible to dissect the functions of genes that govern the development of the parasite. In this study, the polyadenylated transcripts from male and female S. japonicum were isolated for deep sequencing and the sequences were systematically analysed.ResultsFirst, the number of genes actively expressed in the two sexes of S. japonicum was similar, but around 50% of genes were biased to either male or female in expression. Secondly, it was, at the first time, found that more than 50% of the coding region of the genome was transcribed from both strands. Among them, 65% of the genes had sense and their cognate antisense transcripts co-expressed, whereas 35% had inverse relationship between sense and antisense transcript abundance. Further, based on gene ontological analysis, more than 2,000 genes were functionally categorized and biological pathways that are differentially functional in male or female parasites were elucidated.ConclusionsMale and female schistosomal parasites differ in gene expression patterns, many metabolic and biological pathways have been identified in this study and genes differentially expressed in gender specific manner were presented. Importantly, more than 50% of the coding regions of the S. japonicum genome transcribed from both strands, antisense RNA-mediated gene regulation might play a critical role in the parasite biology.

show abstract

Section: Discussionmentioning

confidence: 74%

Global Expression Analysis Revealed Novel Gender-Specific Gene Expression Features in the Blood Fluke Parasite Schistosoma japonicum

et al. 2011

View full text Add to dashboard Cite

show abstract

“…A microarray-based study of Trypanosoma brucei [21] revealed that exposure to thiazolidinediones, and the resultant cellular differentiation, could be attributed to up-regulation of the expression site associated gene 8 (ESAG8). In S. mansoni , genes such as glutathione S -transferase, are up-regulated in response to xenobiotics [22].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Responses of In Vivo Praziquantel Exposure in Schistosomes Identifies a Functional Role for Calcium Signalling Pathway Member CamKII

You

McManus

et al. 2013

PLoS Pathog

View full text Add to dashboard Cite

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” and “Ion Regulation” associated genes. Prominent responses induced in female worms included up-regulation of “Ca2+ Regulation” and “Drug Resistance” genes and later by transcripts of “Detoxification” and “Pathogen Defense” mechanisms. A subset of highly over-expressed genes, with putative drug resistance/detoxification roles or Ca2+-dependant/modulatory functions, were validated by qPCR. The leading candidate among these was CamKII, a putative calcium/calmodulin-dependent protein kinase type II delta chain. RNA interference was employed to knockdown CamKII in S. japonicum to determine the role of CamKII in the response to praziquantel. After partial-knockdown, schistosomes were analysed using IC50 concentrations (50% worm motility) and quantitative monitoring of parasite movement. When CamKII transcription was reduced by 50–69% in S. japonicum, the subsequent effect of an IC50 dosage of praziquantel was exacerbated, reducing motility from 47% to 27% in female worms and from 61% to 23% in males. These observations indicated that CamKII mitigates the effects of praziquantel, probably through stabilising Ca2+ fluxes within parasite muscles and tegument. Together, these studies comprehensively charted transcriptional changes upon exposure to praziquantel and, notably, identified CamKII as potentially central to the, as yet undefined, mode of action of praziquantel.

show abstract

“…The observation that schistosome GSTs could be induced by different xenobiotic compounds in infected animals ( Van de Waa et al, 1993), as were GSTs from other vertebrate or invertebrate species (Clark, 1989), led the authors to propose the existence of conserved mechanisms for GST regulation. However, the fact that the schistosomicidal drug oltipraz, induced GSTs in mouse but diminished GST activity in treated schistosomes, argued against this hypothesis (Nare et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Deletion Analysis of the Schistosoma Mansoni 28‐kDa Glutathione S‐transferase Gene Promoter in Mammalian Cells

Serra

Zemzoumi

Dissous

1997

European Journal of Biochemistry

View full text Add to dashboard Cite

The 1241-bp promoter region of the Schistosoma mansoni 28-kDa glutathione S-transferase gene (Sm28GST) was sequentially deleted and analyzed using the luciferase reporter gene system in different cell lines. The activator protein-I (AP-1) site located at -231 seems to be responsible for the major part of the promoter activity. The 1241-bp Sm28GST promoter was not, in transient transfection experiments, activated by reagents generating reactive oxygen species, such as hydrogen peroxide (Hz02), 3-methylcholanthrene, and ter-methylhydroquinone, but was significantly stimulated by phorbol 12-myristate 13-acetate, a potent protein kinase C activator. The involvement of the -231 AP-1 site in phorbol 12-myristate 13-acetate stimulation was demonstrated. Moreover, evidence for in vitro and in vivo binding of the -231 AP-1 site to JudFos dimers was obtained using mobility gel shift assays and co-transfection of embryonic F9 cells with Jun/Fos expression plasmids, respectively. The presence in S. mansoni nuclear extracts of components with affinity for the AP-1 site suggests conservation of this regulatory pathway in the parasite.

show abstract

Induction of Schistosoma mansoni Glutathione S-Transferase by Xenobiotics

Cited by 17 publications

References 0 publications

Global Expression Analysis Revealed Novel Gender-Specific Gene Expression Features in the Blood Fluke Parasite Schistosoma japonicum

Global Expression Analysis Revealed Novel Gender-Specific Gene Expression Features in the Blood Fluke Parasite Schistosoma japonicum

Transcriptional Responses of In Vivo Praziquantel Exposure in Schistosomes Identifies a Functional Role for Calcium Signalling Pathway Member CamKII

Deletion Analysis of the Schistosoma Mansoni 28‐kDa Glutathione S‐transferase Gene Promoter in Mammalian Cells

Contact Info

Product

Resources

About