Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The emergence and dissemination of drug-resistant malaria parasites represent one of the most important problems in malaria case management. Plasmodium falciparum is the causative agent of the most lethal form of human malaria. The molecular mechanisms that control the life cycle of the malaria parasite are still poorly understood. The published genome sequence (P. falciparum strain 3D7) reveals that several homologs of eukaryotic signaling proteins, such as protein kinases and phosphatases, are conserved in P. falciparum. Proteins kinases are now widely recognized as valuable drug targets in protozoan parasites. In this study, gene silencing with double-stranded RNA (dsRNA) and microarray techniques were used to study the biological function of the cAMP-dependent protein kinase catalytic subunit (PfPKAc) in the parasite erythrocytic life cycle. Treatment of parasites with PfPKAc dsRNA resulted in a marked reduction of endogenous PfPKAc mRNA associated with a compensatory decrease of PfPKAr mRNA followed by morphological changes in schizont stages and cell cycle arrest. The global effects of gene silencing were also investigated using a P. falciparum pan-genomic microarray. Transcriptomic analysis showed that the expression of 329 genes was altered in response to downregulation of PfPKAc mRNA particularly genes in specific metabolic pathways linked with merozoite invasion processes, the calcium/calmodulin signaling, and kinases network and mitochondrial functions.
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PMID:Phenotypic and transcriptomic analyses of Plasmodium falciparum protein kinase A catalytic subunit inhibition. 1977 42

Plasmodium sporozoites invade hepatocytes to initiate infection in the mammalian host. In the infected hepatocytes, sporozoites undergo rapid expansion and differentiation, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Both sporozoites and merozoites invade their host cells by activation of a signaling cascade followed by discharge of micronemal content. cAMP-dependent protein kinase catalytic subunit (PKAc)-mediated signaling plays an important role in merozoite invasion of erythrocytes, but its role during other stages of the parasite remains unknown. Becaused of the essentiality of PKAc in blood stages, we generated conditional mutants of PKAc by disrupting the gene in Plasmodium berghei sporozoites. The mutant salivary gland sporozoites were able to glide, invaded hepatocytes, and matured into hepatic merozoites which were released successfully from merosome, however failed to initiate blood stage infection when inoculated into mice. Our results demonstrate that malaria parasite complete preerythrocytic stages development without PKAc, raising the possibility that the PKAc independent signaling operates in preerythrocytic stages of P. berghei.
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PMID:PKAc is not required for the preerythrocytic stages of Plasmodium berghei. 3114 38