Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.

178 p.

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Bibliographic Details
Main Author:	Sabna Cheemadan
Other Authors:	Zbynek Bozdech
Format:	Theses and Dissertations
Published:	2014
Subjects:	DRNTU::Science::Biological sciences::Cytology
Online Access:	http://hdl.handle.net/10356/57416
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Institution:	Nanyang Technological University

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spelling	sg-ntu-dr.10356-574162023-02-28T18:43:35Z Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum. Sabna Cheemadan Zbynek Bozdech School of Biological Sciences DRNTU::Science::Biological sciences::Cytology 178 p. 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. Doctor of Philosophy (SBS) 2014-04-07T10:31:03Z 2014-04-07T10:31:03Z 2011 2011 Thesis http://hdl.handle.net/10356/57416 Nanyang Technological University application/pdf
institution	Nanyang Technological University
building	NTU Library
continent	Asia
country	Singapore Singapore
content_provider	NTU Library
collection	DR-NTU
topic	DRNTU::Science::Biological sciences::Cytology
spellingShingle	DRNTU::Science::Biological sciences::Cytology Sabna Cheemadan Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
description	178 p.
author2	Zbynek Bozdech
author_facet	Zbynek Bozdech Sabna Cheemadan
format	Theses and Dissertations
author	Sabna Cheemadan
author_sort	Sabna Cheemadan
title	Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
title_short	Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
title_full	Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
title_fullStr	Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
title_full_unstemmed	Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
title_sort	calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.
publishDate	2014
url	http://hdl.handle.net/10356/57416
_version_	1759856285047586816

Calcium ionophores induce transcriptional changes in erythrocytic stages of human malaria parasite plasmodium falciparum.

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