Schistosoma mansoni: functional proteasomes are required for development in the vertebrate host.
Proteasomes are multi-subunit proteases involved in several mechanisms and thought to contribute to the regulation of cellular homeostasis. Here, we report for the first time biochemical evidence for the existence of a ubiquitin-proteasome proteolytic pathway in this parasite. Proteasomes from both cercariae and adult worms exhibited a high preference for hydrolysis of the substrate Suc-LLVY-AMC, although in the cercariae extract the rate of hydrolysis was 50% lower when compared to adult worms extracts. The same difference in proteasome activities was observed when endogenous proteins were broken down in the presence of ATP and ubiquitin. Additionally, accumulation of high molecular weight conjugates was observed when cercariae were pre-incubated with proteasome inhibitors. Finally, we present evidence that during experimental schistosomiasis, proteasome inhibitors were able to reduce the number of lung stage schistosomula, reduce the worm burden and consequently decrease the egg output in infected mice.
Guerra-Sá
R
R
Department of Biological Science, ICEB, Federal University of Ouro Preto, MG, Brazil.
Castro-Borges
W
W
Evangelista
E A
EA
Kettelhut
I C
IC
Rodrigues
V
V
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001700:Biomphalaria; D003374:Coumarins / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology; D006868:Hydrolysis; D007976:Leupeptins / Q000494:pharmacology; D008168:Lung / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D012550:Schistosoma mansoni / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000378:metabolism / Q000469:parasitology*; D025801:Ubiquitin / Q000378:metabolism / Q000494:pharmacology
D003374:Coumarins; D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D025801:Ubiquitin; C089486:carbobenzoxy-leucyl-leucyl-norvalinal; D000255:Adenosine Triphosphate; C046582:succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide; D046988:Proteasome Endopeptidase Complex; C032854:leupeptin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde