Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains

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dc.contributor.advisorSmith, Peter Jen_ZA
dc.contributor.advisorFolb, Peter Ien_ZA
dc.contributor.authorLindt, Meinraden_ZA
dc.date.accessioned2018-01-24T11:50:53Z
dc.date.available2018-01-24T11:50:53Z
dc.date.issued1999en_ZA
dc.description.abstractWorldwide occurrence of chloroquine resistance is an expanding problem in prophylaxis and treatment of malaria. Similarities between the drug resistance phenotype in certain cancers and in malaria suggest that homologue multidrug resistance proteins might be involved in the mechanism of resistance. In this thesis, the expression of a putative multidrug resistance protein of the malaria parasite Plasmodium falciparum, the P-glycoprotein homologue1 (Pgh1), was quantified on food vacuoles, the site of action of chloroquine. Chloroquine susceptibility was determined in 8 different P. falciparum strains. Food vacuoles were isolated from trophozoites of two chloroquine-sensitive (307 and D10) and three chloroquine-resistant (FAC8, K1 and RSA 11) strains. Antibodies against an 18 amino acid long peptide of Pgh1 were raised, as well as two other antibodies against the N-terminal ATP-binding site and the C-terminus of Pgh1. With these antibodies, Pgh1 was detected on isolated food vac.uoles and on trophozoites by immunoblotting. The exact Pgh1 expression levels on food vacuoles were measured with digital image analysis. The chloroquine-sensitive strains 307 and D10 and the chloroquine-resistant strains K1 and RSA 11 expressed equal amounts of Pgh1. The chloroquine-resistant FAC8 strain expressed at least three times more vacuolar Pgh1. No correlation was found between chloroquine IC₅₀ and vacuolar Pgh1 expression levels. Phosphorylation studies on intact food vacuoles indicated that Pgh1 is not a major kinase substrate.en_ZA
dc.identifier.apacitationLindt, M. (1999). <i>Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology. Retrieved from http://hdl.handle.net/11427/26932en_ZA
dc.identifier.chicagocitationLindt, Meinrad. <i>"Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1999. http://hdl.handle.net/11427/26932en_ZA
dc.identifier.citationLindt, M. 1999. Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Lindt, Meinrad AB - Worldwide occurrence of chloroquine resistance is an expanding problem in prophylaxis and treatment of malaria. Similarities between the drug resistance phenotype in certain cancers and in malaria suggest that homologue multidrug resistance proteins might be involved in the mechanism of resistance. In this thesis, the expression of a putative multidrug resistance protein of the malaria parasite Plasmodium falciparum, the P-glycoprotein homologue1 (Pgh1), was quantified on food vacuoles, the site of action of chloroquine. Chloroquine susceptibility was determined in 8 different P. falciparum strains. Food vacuoles were isolated from trophozoites of two chloroquine-sensitive (307 and D10) and three chloroquine-resistant (FAC8, K1 and RSA 11) strains. Antibodies against an 18 amino acid long peptide of Pgh1 were raised, as well as two other antibodies against the N-terminal ATP-binding site and the C-terminus of Pgh1. With these antibodies, Pgh1 was detected on isolated food vac.uoles and on trophozoites by immunoblotting. The exact Pgh1 expression levels on food vacuoles were measured with digital image analysis. The chloroquine-sensitive strains 307 and D10 and the chloroquine-resistant strains K1 and RSA 11 expressed equal amounts of Pgh1. The chloroquine-resistant FAC8 strain expressed at least three times more vacuolar Pgh1. No correlation was found between chloroquine IC₅₀ and vacuolar Pgh1 expression levels. Phosphorylation studies on intact food vacuoles indicated that Pgh1 is not a major kinase substrate. DA - 1999 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1999 T1 - Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains TI - Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains UR - http://hdl.handle.net/11427/26932 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/26932
dc.identifier.vancouvercitationLindt M. Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1999 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/26932en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherPharmacologyen_ZA
dc.titleExpression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strainsen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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