scholarly journals Sterigmatocystin Limits Plasmodium falciparum Proliferation and Transmission

2021 ◽  
Vol 14 (12) ◽  
pp. 1238
Author(s):  
Guodong Niu ◽  
Komal Kalani ◽  
Xiaohong Wang ◽  
Jun Li
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Mechanisms ◽  
Human Kidney ◽  
Kidney Cells ◽  
Penicillium Janthinellum ◽  
Chromatographic Techniques ◽  
Membrane Feeding ◽  
Drug Lead ◽  
Drug Discovery Program ◽  
Stage Parasite

As part of our drug discovery program against malaria, the Penicillium janthinellum extract was discovered to inhibit P. falciparum proliferation in blood and transmission to mosquitoes. Bioactivity-guided fractionation of P. janthinellum extraction was carried out using chromatographic techniques. We determined the activities of fractions against Plasmodium falciparum asexual stage parasite proliferation in culture and sexual stage parasite transmission to mosquitoes using standard membrane feeding assays (SMFA). One active compound was isolated. Based on mass spectrometry and nuclear magnetic resonance profiles, the compound was structurally determined to be sterigmatocystin. Sterigmatocystin inhibited P. falciparum proliferation in the blood with an IC50 of 34 µM and limited the sexual parasites to infect mosquitoes with an IC50 of 48 µM. Meanwhile, sterigmatocystin did not show any acute toxicity to human kidney cells at a concentration of 64 µM or lower. Sterigmatocystin can be used as a drug lead for malaria control and as a probe to understand molecular mechanisms of malaria transmission.

1107: Evaluation of Cystine Transport in Cultured Human Kidney Cells: Primer to Gene Therapy of Cystinuria

2005 ◽  
Vol 173 (4S) ◽  
pp. 300-300
Author(s):  
Sreedhar Sagi ◽  
Lutz Trojan ◽  
Peter Aiken ◽  
Maurice S. Michel ◽  
Thomas Knoll
Keyword(s):  
Gene Therapy ◽  
Human Kidney ◽  
Kidney Cells

scholarly journals Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Koudraogo Bienvenue Yaméogo ◽  
Rakiswendé Serge Yerbanga ◽  
Seydou Bienvenu Ouattara ◽  
Franck A. Yao ◽  
Thierry Lefèvre ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Life History Traits ◽  
Controlled Trial ◽  
Double Blind ◽  
Membrane Feeding ◽  
Seasonal Malaria Chemoprevention ◽  
Negative Effect ◽  
Transmission Period ◽  
Membrane Feeding Assay

Abstract Background Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. Methods The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. Results The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P < 0.0001) and the gametocyte prevalence (LRT X22 = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X22 = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X22 = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P < 0.0001). Conclusion This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

Cellular and molecular mechanisms of bromate-induced cytotoxicity in human and rat kidney cells

Toxicology ◽  
2010 ◽  
Vol 269 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Xiaoling Zhang ◽  
Dilhara De Silva ◽  
Bin Sun ◽  
Jeffery Fisher ◽  
Richard J. Bull ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rat Kidney ◽  
Kidney Cells

Poly(ADP-ribosyl)ation of mannose-binding lectin out of human kidney cells

2011 ◽  
Vol 352 (1-2) ◽  
pp. 231-238 ◽  
Author(s):  
Natalie N. Sidorova ◽  
Svetlana Yu. Kurchashova ◽  
Tural Ya. Yarahmedov ◽  
Rustam H. Ziganshin ◽  
Alexander N. Kuimov
Keyword(s):  
Human Kidney ◽  
Mannose Binding Lectin ◽  
Kidney Cells ◽  
Mannose Binding ◽  
Binding Lectin

Cloning, characterization, and gene organization of K-Cl cotransporter from pig and human kidney and C. elegans

1998 ◽  
Vol 275 (4) ◽  
pp. F550-F564 ◽  
Author(s):  
Eli J. Holtzman ◽  
Sumit Kumar ◽  
Carol A. Faaland ◽  
Fern Warner ◽  
Paul J. Logue ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Kidney ◽  
Gene Organization ◽  
Kidney Cells ◽  
Hek 293 ◽  
Human Embryonic Kidney Cells ◽  
C Elegans ◽  
Transmembrane Segments ◽  
Extracellular Loops ◽  
Stimulation Of

We isolated and characterized the cDNAs for the human, pig, and Caenorhabditis elegansK-Cl cotransporters. The pig and human homologs are 94% identical and contain 1,085 and 1,086 amino acids, respectively. The deduced protein of the C. elegans K-Cl cotransporter clone (CE-KCC1) contains 1,003 amino acids. The mammalian K-Cl cotransporters share ∼45% similarity with CE-KCC1. Hydropathy analyses of the three clones indicate typical KCC topology patterns with 12 transmembrane segments, large extracellular loops between transmembrane domains 5 and 6 (unique to KCC), and large COOH-terminal domains. Human KCC1 is widely expressed among various tissues. This KCC1 gene spans 23 kb and is organized in 24 exons, whereas the CE-KCC1 gene spans 3.5 kb and contains 10 exons. Transiently and stably transfected human embryonic kidney cells (HEK-293) expressing the human, pig, and C. elegans K-Cl cotransporter fulfilled two (pig) or five (human and C. elegans) criteria for increased expression of the K-Cl cotransporter. The criteria employed were basal K-Cl cotransport; stimulation of cotransport by swelling, N-ethylmaleimide, staurosporine, and reduced cell Mg concentration; and secondary stimulation of Na-K-Cl cotransport.

scholarly journals Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies

2021 ◽  
Vol 17 (4) ◽  
pp. e1008067
Author(s):  
Lisette Meerstein-Kessel ◽  
Jeron Venhuizen ◽  
Daniel Garza ◽  
Nicholas I. Proellochs ◽  
Emma J. Vos ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Salivary Glands ◽  
Molecular Mechanisms ◽  
Life Stage ◽  
Acid Synthesis ◽  
Complex Life Cycle ◽  
Quiescent State ◽  
Extended Phase ◽  
Human Host ◽  
Falciparum Sporozoite

Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and proteomics studies and is also targeted by the most advanced malaria vaccine. We applied Bayesian data integration to determine which proteins are not only present in sporozoites but are also specific to that stage. Transcriptomic and proteomic Plasmodium data sets from 26 studies were weighted for how representative they are for sporozoites, based on a carefully assembled gold standard for Plasmodium falciparum (Pf) proteins known to be present or absent during the sporozoite life stage. Of 5418 Pf genes for which expression data were available at the RNA level or at the protein level, 975 were identified as enriched in sporozoites and 90 specific to them. We show that Pf sporozoites are enriched for proteins involved in type II fatty acid synthesis in the apicoplast and GPI anchor synthesis, but otherwise appear metabolically relatively inactive in the salivary glands of mosquitos. Newly annotated hypothetical sporozoite-specific and sporozoite-enriched proteins highlight sporozoite-specific functions. They include PF3D7_0104100 that we identified to be homologous to the prominin family, which in human has been related to a quiescent state of cancer cells. We document high levels of genetic variability for sporozoite proteins, specifically for sporozoite-specific proteins that elicit antibodies in the human host. Nevertheless, we can identify nine relatively well-conserved sporozoite proteins that elicit antibodies and that together can serve as markers for previous exposure. Our understanding of sporozoite biology benefits from identifying key pathways that are enriched during this life stage. This work can guide studies of molecular mechanisms underlying sporozoite biology and potential well-conserved targets for marker and drug development.

scholarly journals Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hanh Thi-Kim Vu ◽  
Jochen C Rink ◽  
Sean A McKinney ◽  
Melainia McClain ◽  
Naharajan Lakshmanaperumal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Human Kidney ◽  
Cyst Formation ◽  
Cystic Kidney ◽  
Flow Sensing ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Genetic Interference ◽  
Cystic Kidney Diseases

Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (Caenorhabditis elegans and Drosophila melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.

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