Schistosoma mansoni: Influence of the female parasite on glutathione biosynthesis in the male

1989 ◽  
Vol 69 (1) ◽  
pp. 116-124 ◽  
Author(s):  
David A. Siegel ◽  
James W. Tracy
1989 ◽  
Vol 257 (3) ◽  
pp. R618-R625 ◽  
Author(s):  
E. A. Vandewaa ◽  
G. Mills ◽  
G. Z. Chen ◽  
L. A. Foster ◽  
J. L. Bennett

Pathological lesions observed in humans infected with Schistosoma mansoni are due to the eggs produced by the female parasite. Mevinolin, a potent inhibitor of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase, blocks egg production by this parasite. In this report, we demonstrate that cholesterol precursors, mevalonate and farnesol, stimulate egg production by the female parasite and that these precursors can reverse the mevinolin-induced inhibition of egg production. Because the parasite cannot synthesize cholesterol, we incubated parasites in a culture media containing radiolabeled acetate with and without mevinolin. We isolated nonsterol lipids from the parasite and observed that mevinolin dramatically reduced the conversion of acetate into the polyisoprenoid (dolichols) lipids of the parasite. Dolichols and other nonsterol lipids did not stimulate egg production. HMG-CoA reductase activity was observed in homogenates of the parasite and was inhibited by mevinolin (Ki = 52 nM), but its activity was tripled when the parasite was chronically exposed to low doses of the drug. Parasites with increased reductase activity produced five to six times more eggs. Lastly, chronic administration of large doses of mevinolin to infected mice resulted in a marked reduction of the pathology associated with the infection. These results suggest that egg production in S. mansoni is associated with the parasite's HMG-CoA reductase activity and that a nonsterol lipid produced in the biochemical pathway regulated by this enzyme stimulates egg production.


Author(s):  
Betty Ruth Jones ◽  
Steve Chi-Tang Pan

INTRODUCTION: Schistosomiasis has been described as “one of the most devastating diseases of mankind, second only to malaria in its deleterious effects on the social and economic development of populations in many warm areas of the world.” The disease is worldwide and is probably spreading faster and becoming more intense than the overall research efforts designed to provide the basis for countering it. Moreover, there are indications that the development of water resources and the demands for increasing cultivation and food in developing countries may prevent adequate control of the disease and thus the number of infections are increasing.Our knowledge of the basic biology of the parasites causing the disease is far from adequate. Such knowledge is essential if we are to develop a rational approach to the effective control of human schistosomiasis. The miracidium is the first infective stage in the complex life cycle of schistosomes. The future of the entire life cycle depends on the capacity and ability of this organism to locate and enter a suitable snail host for further development, Little is known about the nervous system of the miracidium of Schistosoma mansoni and of other trematodes. Studies indicate that miracidia contain a well developed and complex nervous system that may aid the larvae in locating and entering a susceptible snail host (Wilson, 1970; Brooker, 1972; Chernin, 1974; Pan, 1980; Mehlhorn, 1988; and Jones, 1987-1988).


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
AIO Salloum ◽  
R Lucarini ◽  
MG Tozatti ◽  
J Medeiros ◽  
MLA Silva ◽  
...  

2019 ◽  
Author(s):  
M Roderfeld ◽  
J Lichtenberger ◽  
F Wolters ◽  
T Quack ◽  
CG Grevelding ◽  
...  
Keyword(s):  

2020 ◽  
Author(s):  
SM Gindner ◽  
V von Bülow ◽  
L Hehr ◽  
N Buß ◽  
G Schramm ◽  
...  
Keyword(s):  

2004 ◽  
Vol 39 (02) ◽  
pp. 137
Author(s):  
Francisco Javier Carod Artal ◽  
Antonio Pedro Vargas
Keyword(s):  

2013 ◽  
Vol 4 ◽  
Author(s):  
Xavier Aurelizia Maria ◽  
Tavares Daniel ◽  
Guimar�es Erick ◽  
Da Silva Antonio Carlos ◽  
De Moraes Neto Antonio Henrique

Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>


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