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Antimalarial drug heat shock protein 70

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https://www.readbyqxmd.com/read/26156578/immunophilin-protein-interactions-in-plasmodium-falciparum
#1
Darren Leneghan, Angus Bell
Immunophilins comprise two protein families, cyclophilins (CYPs) and FK506-binding proteins (FKBPs), and are the major receptors for the immunosuppressive drugs cyclosporin A (CsA) and FK506 (tacrolimus), respectively. Most eukaryotic species have at least one immunophilin and some of them have been associated with pathogenesis of infectious or parasitic diseases or the action of antiparasitic drugs. The human malarial parasite Plasmodium falciparum has 13 immunophilin or immunophilin-like genes but the functions of their products are unknown...
September 2015: Parasitology
https://www.readbyqxmd.com/read/24854538/selective-modulation-of-plasmodial-hsp70s-by-small-molecules-with-antimalarial-activity
#2
Ingrid L Cockburn, Aileen Boshoff, Eva-Rachele Pesce, Gregory L Blatch
Plasmodial heat shock protein 70 (Hsp70) chaperones represent a promising new class of antimalarial drug targets because of the important roles they play in the survival and pathogenesis of the malaria parasite Plasmodium falciparum. This study assessed a set of small molecules (lapachol, bromo-β-lapachona and malonganenones A, B and C) as potential modulators of two biologically important plasmodial Hsp70s, the parasite-resident PfHsp70-1 and the exported PfHsp70-x. Compounds of interest were assessed for modulatory effects on the steady-state basal and heat shock protein 40 (Hsp40)-stimulated ATPase activities of PfHsp70-1, PfHsp70-x and human Hsp70, as well as on the protein aggregation suppression activity of PfHsp70-x...
November 1, 2014: Biological Chemistry
https://www.readbyqxmd.com/read/21426241/screening-for-small-molecule-modulators-of-hsp70-chaperone-activity-using-protein-aggregation-suppression-assays-inhibition-of-the-plasmodial-chaperone-pfhsp70-1
#3
Ingrid L Cockburn, Eva-Rachele Pesce, Jude M Pryzborski, Michael T Davies-Coleman, Peter G K Clark, Robert A Keyzers, Linda L Stephens, Gregory L Blatch
Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1...
May 2011: Biological Chemistry
https://www.readbyqxmd.com/read/19523215/the-effect-of-mimicking-febrile-temperature-and-drug-stress-on-malarial-development
#4
Ratchaneewan Aunpad, Sangdao Somsri, Kesara Na-Bangchang, Rachanee Udomsangpetch, Mathirut Mungthin, Poom Adisakwattana, Wanna Chaijaroenkul
BACKGROUND: Malaria remains one of the most important tropical diseases of human with 1-2 million deaths annually especially caused by P. falciparum. During malarial life cycle, they exposed to many environmentally stresses including wide temperature fluctuation and pharmacological active molecules. These trigger malarial evolutionarily adaptive responses. The effect of febrile temperature on malarial growth, development and drug susceptibility by mimicking patient in treatment failure before and after drug uptake was examined...
2009: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/19480682/co-ordinated-stage-dependent-enhancement-of-plasmodium-falciparum-antioxidant-enzymes-and-heat-shock-protein-expression-in-parasites-growing-in-oxidatively-stressed-or-g6pd-deficient-red-blood-cells
#5
Oscar Bate Akide-Ndunge, Elisa Tambini, Giuliana Giribaldi, Paul J McMillan, Sylke Müller, Paolo Arese, Francesco Turrini
BACKGROUND: Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense...
2009: Malaria Journal
https://www.readbyqxmd.com/read/12669348/the-treatment-of-plasmodium-falciparum-infected-erythrocytes-with-chloroquine-leads-to-accumulation-of-ferriprotoporphyrin-ix-bound-to-particular-parasite-proteins-and-to-the-inhibition-of-the-parasite-s-6-phosphogluconate-dehydrogenase
#6
O Famin, H Ginsburg
Ferriprotoporphyrin IX (FPIX) is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins...
March 2003: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/9607637/4-aminoquinoline-antimalarials-enhance-uv-b-induced-c-jun-transcriptional-activation
#7
T Q Nguyen, J D Capra, R D Sontheimer
Previous work has documented that the earliest observable response in mammalian cells following ultraviolet (UV) irradiation is the activation of plasma membrane-associated Src tyrosine kinases. These molecules then trigger a signalling cascade that results in activation of the transcription factor AP-1 which subsequently transactivates the early immediate genes including c-jun. This pathway has been postulated to play a protective role against UV damage. As aminoquinoline antimalarials such as chloroquine are known to downregulate several photoinduced cutaneous disorders including LE-specific skin disease, we asked whether chloroquine might be capable of modulating this early limb of the UV light response...
1998: Lupus
https://www.readbyqxmd.com/read/1869355/lack-of-correlation-between-red-cell-invasion-by-merozoites-and-anti-heat-shock-protein-70-antibody-levels-in-malaria-patients-sera
#8
S Biswas, Y D Sharma
A total of 172 sera samples were collected from individuals who were living in Piyawli-Jaitwarpur village in Ghaziabad district (U.P.), India. They had suffered from falciparum malaria attack, and were cured with antimalarial drugs 1-2 weeks prior to sample collection. These samples were divided into nine groups according to their age. The pooled sera from each group were tested for the presence of anti-schizont and anti-heat shock protein (hsp)-70 antibodies, as well as for parasite growth inhibition in vitro...
April 1991: International Journal for Parasitology
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