Pyronaridine and chloroquine responses in the K1 strain
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium falciparum
PROVIDER: GSE30867 | GEO | 2011/08/02
SECONDARY ACCESSION(S): PRJNA154593
REPOSITORIES: GEO
Similar Datasets
Project description:Pyronaridine (PN) and chloroquine (CQ) are structurally related anti-malarial drugs with primarily the same mode of action. However, PN is effective against several multidrug-resistant lines of Plasmodium falciparum, including CQ-resistant lines, suggestive of important operational differences between the two drugs. Synchronized trophozoite-stage cultures of P. falciparum strain K1 (CQ resistant) were exposed to 50% inhibitory concentrations (IC50) of PN and CQ, and parasites were harvested from culture after 4 and 24 hours exposure. Global transcriptional changes effected by drug treatment were investigated using DNA microarrays. Plasmodium falciparum in vitro cultures were synchronized to trophozoite stage (22-24h post infection) and exposed to either CQ or PN at IC50 concentrations. 18 sample pairs (drug treated/untreated) were analyzed; 9 for CQ and 9 for PN. All drug-treated samples were labelled with Cy5 and untreated controls were labelled with Cy3.
2011-08-01 | E-GEOD-30867 | biostudies-arrayexpress
Project description:To identify the developmentally regulated genes, which could confound identification of PN and CQ drug responsive genes, RNA samples from drug-free synchronized cultures from ring, trophozoite, and schizont stages were individually labelled and hybridized with a pooled sample from the three stages. The data from this experiment were used to compare the developmental profile of the K1 strain with the data from other P. falciparum strains. 9 samples were obtained from three developmental stages of parasite development (3 each from ring, trophozoite and schizont synchronized parasites). Three independent cultures were obtained, synchronized on different days.
2011-08-01 | E-GEOD-30869 | biostudies-arrayexpress
Project description:To identify the developmentally regulated genes, which could confound identification of PN and CQ drug responsive genes, RNA samples from drug-free synchronized cultures from ring, trophozoite, and schizont stages were individually labelled and hybridized with a pooled sample from the three stages. The data from this experiment were used to compare the developmental profile of the K1 strain with the data from other P. falciparum strains.
2011-08-02 | GSE30869 | GEO
Project description:Chloroquine (CQ) could function as a lysosomotropic inhibitor to impair the autophagy-lysosome pathway, and is widely used to treat malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear.;Here we showed that CQ treatment reduced iSCs viability in a dose-dependent manner. CQ treatment (20µM) of iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis. Melatonin (MT) (10nM) could partially rescue CQ-induced phenotypic defects. Transcriptome profiling (RNA-seq) identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20µM CQ vs. DMSO control group), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, MT addition identified only 467 (224 up- and 243 down-regulated) DEGs (CQ+MT vs. DMSO), enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction, respectively.Collectively, CQ treatment could impair porcine iSC viability by deranging apoptosis- and autophagy related signaling pathways, which could be partially rescued by MT supplementation.
2024-07-06 | GSE180995 | GEO
Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5’ upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut.
2013-02-07 | GSE44128 | GEO
Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5’ upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut.
2013-02-07 | GSE44127 | GEO
Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5M-bM-^@M-^Y upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut. 2 P. falciparum lab clones derived from 3D7 strain were harvested during the intra-erythrocytic cycle for genomic DNA. gDNA were extracted by phenol chloroform. Synthesis of labelled target DNA was carried out as previously described: Bozdech, Z., M. Llinas, B. L. Pulliam, E. D. Wong, J. Zhu & J. L. DeRisi, (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol 1: E5, and used in comparative genomic microarray hybridizations (CGH).
2013-02-07 | E-GEOD-44128 | biostudies-arrayexpress
Project description:Drug resistance in Plasmodium falciparum remains a challenge for the malaria eradication programs around the world. With the emergence of artemisinin resistance, the efficacy of the partner drugs in the artemisinin combination therapies (ACT) that include quinoline based drugs is becoming critical. So far only few resistance markers have been identified and verified from which only two ABC transmembrane transporters namely PfMDR1 and PfCRT have been experimentally verified. Another P. falciparum ABC transporter, the multidrug resistance-associated protein (PfMRP2) represents an additional possible factor of drug resistance in P. falciparum. In this study, we identify a parasite clone that is derived from the 3D7 P. falciparum strain and which shows increased resistance to chloroquine and mefloquine through the trophozoite and schizont stages. We demonstrate that the resistance phenotype is caused by a 4.1 kb deletion in the 5M-bM-^@M-^Y upstream region of the pfmrp2 gene that leads to an alteration in the pfmrp2 transcription that result in increased levels of PfMRP2 protein. These results also suggest the importance of putative promoter elements in regulation of gene expression during the P. falciparum intra-erythrocytic developmental cycle and the potential of such genetic polymorphisms to underlie drug resistance phenotypes. Presented here are the data from microarray-based genome-wide transcriptomic and genomic studies of the drug-sensitive and drug-resistant 3D7 clones 11C/wt and 6A/mut. 2 P. falciparum lab clones derived from 3D7 strain were harvested during the intra-erythrocytic cycle at 8hr intervals over 48 hours to obtain a total of 6 time point samples per clone. RNA from a total of 12 samples were extracted. Synthesis of target DNA was carried out as described in Bozdech, Z., S. Mok & A. P. Gupta, (2013) DNA microarray-based genome-wide analyses of Plasmodium parasites. Methods in molecular biology 923: 189-211 and used in replicate microarray hybridizations against a common RNA reference pool of 3D7 strain.
2013-02-07 | E-GEOD-44127 | biostudies-arrayexpress
Project description:The main goal of this study is to characterize the transcriptional modulations induced by antiviral compounds derived from chloroquine on Huh7 cells infected with HCV. And thus to identify among the genes modulated by infection, those who are regulated by chloroquine and potentially involved in the antiviral activity of the compound.Two HCV cell models were used: a non-infectious HCV replicon and the infectious HCV cell culture (HCVcc). In addition, this study aimed to highlight the characteristics of derivatives of antiviral chloroquine, compared with chloroquine itself. Abstract from the associated publication: Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portion of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Indeed, infection with hepatitis C virus (HCV) was shown to induce autophagy through ER stress signaling and subsequent Unfolded Protein Response (UPR) activation. Moreover, a role of autophagy in promoting HCV infection has been suggested and chloroquine (CQ), a lysosomal protease inhibitor, has been seen blocking autophagy as well as inhibiting HCV replication. In the present report, mechanisms accounting for these inhibitory effects were investigated. Gene expression profiling was performed on CQ treated JFH-1-infected Huh7 cells to identify the host cellular genes that are transcriptionally regulated by infection, and silenced by CQ-based treatment. Herein, we demonstrate that CQ reduces the expression of genes induced by the viral infection such as those encoding autophagic key factors triggering the turn-off of mTOR activity as well as factors involved in p53 and NF-KappaB activities. However, we present several lines of evidence demonstrating that the CQ repressive effect observed on the HCV-induced pathways results from a decrease of ER stress due to the upstream pH-dependent inhibitory effect of CQ on viral replication.
2012-07-01 | GSE30351 | GEO
Project description:The main goal of this study is to characterize the transcriptional modulations induced by antiviral compounds derived from chloroquine on Huh7 cells infected with HCV. And thus to identify among the genes modulated by infection, those who are regulated by chloroquine and potentially involved in the antiviral activity of the compound.Two HCV cell models were used: a non-infectious HCV replicon and the infectious HCV cell culture (HCVcc). In addition, this study aimed to highlight the characteristics of derivatives of antiviral chloroquine, compared with chloroquine itself. Abstract from the associated publication: Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portion of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Indeed, infection with hepatitis C virus (HCV) was shown to induce autophagy through ER stress signaling and subsequent Unfolded Protein Response (UPR) activation. Moreover, a role of autophagy in promoting HCV infection has been suggested and chloroquine (CQ), a lysosomal protease inhibitor, has been seen blocking autophagy as well as inhibiting HCV replication. In the present report, mechanisms accounting for these inhibitory effects were investigated. Gene expression profiling was performed on CQ treated JFH-1-infected Huh7 cells to identify the host cellular genes that are transcriptionally regulated by infection, and silenced by CQ-based treatment. Herein, we demonstrate that CQ reduces the expression of genes induced by the viral infection such as those encoding autophagic key factors triggering the turn-off of mTOR activity as well as factors involved in p53 and NF-KappaB activities. However, we present several lines of evidence demonstrating that the CQ repressive effect observed on the HCV-induced pathways results from a decrease of ER stress due to the upstream pH-dependent inhibitory effect of CQ on viral replication. Gene expression modulations were measured in Huh7 harboring replicon cells stimulated with a 10M-BM-5M of a Chloroquine derivative compound called CQd, during 6h, 12h and 24h. Two independent experiments were performed at each time. An untreated control condition was performed in each experiment, expression was measured at the 24h time point. For the HCVcc model, gene expression analysis was analyzed in two conditions: infection and treatment of infected cells. To characterize modulations in time course of infection, Huh7 naM-CM-/ve cells were infected with JFH1/CS-N6-A4 viral stock and gene expression was measured at 6h, 24h and 48h postinfection. For each kinetic time point, an uninfected condition was performed and gene expression was measured. An additional control testing the interferon (IFN) induced modulations on infected cells was included and gene expression was measured after a 48h stimulation with 100 IU of IFN (alpha 2 b). To characterize the antiviral modulations resulting from treatment with Chloroquine (CQ) or a derivative compound (CQd), gene expression was measured in JFH1/CS-N6-A4 infected Huh7 cells treated with 40M-BM-5M of CQ or CQd during 12h or 48h post-treatment and infection. For each kinetic time point 12h and 48h, an untreated infected control was also performed and gene expression measured.
2012-06-30 | E-GEOD-30351 | biostudies-arrayexpress