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|Title:||Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.||Authors:||Sabna Cheemadan||Keywords:||DRNTU::Science::Biological sciences::Cytology||Issue Date:||2011||Abstract:||Calcium is a universal second messenger molecule that plays a significant role in several biological processes. Presence of calcium sensors (calmodulins) and calcium dependent protein kinases in Plasmodium species suggest an important role of calcium dependent signaling pathways in the regulation of cellular processes in the malaria parasites. In general, changes in the intracellular calcium ion levels are interpreted as a signal that mediates biological processes varying from transcription to secretion. It was shown that in Plasmodium falciparum the intracellular calcium concentration rises as a result of exposure of the parasite cells to calcium ionophores (2-3). In this study, parasite response to calcium ionophores (ionomycin and A23187) and calcium channel blockers (thapsigargin and verapamil) was analyzed using DNA microarray. Global changes in various mRNA abundance levels have been analyzed and several pathways were found to be affected in the calcium ionophore treated parasites. Calcium channel blockers did not show any major effect. Interestingly, the treatment with calcium ionophores resulted in a significant down regulation of essentially all the protein-coding genes of the apicoplast genome. The effect of ionomycin was particularly commendable as it was more specific when compared to the wide range changes caused by A23187. Chelation of extracellular Ca2+ using EGTA still produced the same effect suggesting that external Ca2+ influx is not responsible for the apicoplast gene down regulation. Underlining the involvement of intracellular Ca2+ in this process, a nuclear encoded apicoplast targeted protein with an EF-hand domain was identified and localized to the apicoplast. Reduced sensitivity towards ionomycin was observed in the parasites expressing this protein suggesting its possible involvement in the phenomenon. Apicoplast enriched fractions isolated from the ionomycin treated cells was subjected to proteomic analysis using 2-D DIGE and a few non-apicoplast proteins were found to be down-regulated whose significance in the context of ionomycin treatment needs further exploration.||Description:||178 p.||URI:||http://hdl.handle.net/10356/57416||Rights:||Nanyang Technological University||Fulltext Permission:||restricted||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Theses|
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