Detection and Localization of a Ca2+-ATPase Activity in Toxoplasma gondii.

Bouchot, André; Jaillet, Jean-David; Bonhomme, A.; Alessandro, Nathalie Pezzella-D'; Laquerrière, Patrice; Kilian, Laurence; Burlet, Henriette; Gómez-Marín, Jorge Enrique; Pluot, M; Bonhomme, Pierre; Pinon, J. M.

doi:10.1247/csf.26.49

Cited by 10 publications

(4 citation statements)

References 54 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the electron‐dense appearance in the lumen of these two subdomains suggests that the cargoes are more condensed, non‐partitioning of DAMP may reflect the novel rhoptry content, which is presumed to be a tightly packaged gel of proteins and lipids. Cytochemical studies also suggest that rhoptries contain an acidic phosphatase and Ca 2+ ‐, Mg 2+ ‐ATPase activities, as well as a high concentration of calcium (Bouchot et al ., 2001).…”

Section: Rhoptry Proteins Are Processed In An Acidified Lumenmentioning

confidence: 99%

Are rhoptries in Apicomplexan parasites secretory granules or secretory lysosomal granules?

Ngô

Yang

Joiner

2004

Molecular Microbiology

View full text Add to dashboard Cite

SummaryThe club-shaped rhoptries in Apicomplexan parasites are one of the most unusual secretory organelles among the eukaryotes, containing unusual lipid and protein cargo that is specialized for intracellular parasitism. Rhoptries have traditionally been viewed strictly as regulated secretory granules. We discuss in this article recent data on the cargo, function and biogenesis of rhoptries in two parasitic model systems, Toxoplasma and Plasmodium . Current findings suggest that rhoptries receive products from both biosynthetic and endocytic pathways and, therefore, they are most analogous to secretory lysosomal granules found in mammalian cells.

show abstract

Section: Rhoptry Proteins Are Processed In An Acidified Lumenmentioning

confidence: 99%

Are rhoptries in Apicomplexan parasites secretory granules or secretory lysosomal granules?

Ngô

Yang

Joiner

2004

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Deoxyartemisinins lacking the 1,2,4-trioxane moiety are unable to effectively block intracellular Toxoplasma tachyzoite replication but can moderately inhibit extracellular tachyzoite invastion of host cells . Thus the illumination of the exact mechanism of action of artemisinins against in vitro Toxoplasma is still an area of intense interest and investigation. − Additionally, thiazole-containing compounds have been shown, in vitro, to possess antimicrobial and antiparasitic properties. , We have previously shown, in vitro, that some C9−C10 dehydroartemsinin (DART) derivatives, including one possessing a thiazole moiety, inhibit multiple steps in the lytic cycle of T. gondii . This report describes results with novel DART-thiazole, DART-oxadiazole, and DART-carboxamide derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…24 Thus the illumination of the exact mechanism of action of artemisinins against in vitro Toxoplasma is still an area of intense interest and investigation. [25][26][27][28] Additionally, thiazole-containing compounds have been shown, in vitro, to possess antimicrobial 29 and antiparasitic properties. 30,31 We have previously shown, in vitro, that some C9-C10 dehydroartemsinin (DART) derivatives, including one possessing a thiazole moiety, inhibit multiple steps in the lytic cycle of T. gondii.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thiazole, Oxadiazole, and Carboxamide Derivatives of Artemisinin are Highly Selective and Potent Inhibitors of Toxoplasma gondii

et al. 2010

View full text Add to dashboard Cite

We have prepared 23 new dehydroartemisinin (DART) trioxane derivatives (11 thiazoles, 2 oxadiazoles, and 10 carboxamides) and have screened them for in vitro activity in the Toxoplasma lytic cycle. Fifteen (65%) of the derivatives were non-cytotoxic to host cells (TD50 ≥ 320 μM). Eight thiazole derivatives and two carboxamide derivatives displayed effective inhibition of Toxoplasma growth (IC50 = 0.25-0.42 μM), comparable in potency to artemether (IC50 = 0.31 μM) and >100 times more inhibitory than the currently employed front-line drug trimethoprim (IC50 = 46 μM). The thiazoles as a group were more effective than the other derivatives at inhibiting growth of extracellular as well as intracellular parasites. Unexpectedly, two thiazole trioxanes (5 and 6) were parasiticidal; both inhibited parasite replication irreversibly after parasite exposure to 10 μM of drug for 24 hours, whereas the standard trioxane drugs artemisinin and artemether were not parasiticidal. Some of the new derivatives of artemisinin described here represent effective anti-Toxoplasma trioxanes as well as molecular probes for elucidating the mechanism of action of the DART class of artemisinin derivatives.

show abstract

Calcium Regulation and Signaling in Apicomplexan Parasites

Nagamune

Moreno

Chini

et al.

Subcellular Biochemistry

101

View full text Add to dashboard Cite

A picomplexan parasites rely on calcium-mediated signaling for a variety of vital functions including protein secretion, motility, cell invasion, and differentiation. These functions are controlled by a variety of specialized systems for uptake and release of calcium, which acts as a second messenger, and on the functions of calcium-dependent pro› teins. Defining these systems in parasites has been complicated by their evolutionary dis› tance from model organisms and practical concerns in working with small, and somewhat fastidious cells. Comparative genomic analyses of Toxoplasma gondii, Plasmodium spp. and Cryptosporidium spp. reveal several interesting adaptations for calcium-related processes in parasites. Apicomplexans contain several P-type Ca ^ ATPases including an ER-type reuptake mechanism (SERCA), which is the proposed target of artemisinin. All three organisms also contain several genes related to Golgi PMR-like calcium transporters, and a Ca^VH^ ex› changer, while plasma membrane-type (PMCA) Ca'^^ ATPases and voltage-dependent cal› cium channels are exclusively found in T gondii. Pharmacological evidence supports the presence of IP3 and ryanodine channels for calcium-mediated release. Collectively these sys› tems regulate calcium homeostasis and release calcium to act as a signal. Downstream re› sponses are controlled by a family of EF-hand containing calcium binding proteins includ› ing calmodulin, and an array of centrin and caltractin-like genes. Most surprising, apicomplexans contain a diversity of calcium-dependent protein kinases (CDPK), which are commonly found in plants. Toxoplasma contains more than 20 CDPK or CDPK-like pro› teases, while Plasmodium and Cryptosporidium have fewer than half this number. Several of these CDPKs have been shown to play vital roles in protein secretion, invasion, and differen› tiation, indicating that disruption of calcium-regulated pathways may provide a novel means for selective inhibition of parasites. Defining Calcium Regulation in an Early Branching EukaryoteApicomplexan parasites are most similar to ciliates and dinoflagellates and only distandy related to plants, fungi, and animals typically used as model organisms. Apicomplexans con› tain a remnant plastid derived from a secondary endosymbiont, called the apicoplast. A num› ber of plant-like metabolic systems are found in apicomplexans either due to retention of *Corresponding

show abstract

Detection and Localization of a Ca2+-ATPase Activity in Toxoplasma gondii.

Cited by 10 publications

References 54 publications

Are rhoptries in Apicomplexan parasites secretory granules or secretory lysosomal granules?

Are rhoptries in Apicomplexan parasites secretory granules or secretory lysosomal granules?

Thiazole, Oxadiazole, and Carboxamide Derivatives of Artemisinin are Highly Selective and Potent Inhibitors of Toxoplasma gondii

Calcium Regulation and Signaling in Apicomplexan Parasites

Contact Info

Product

Resources

About