TY - JOUR
T1 - Plasmodium falciparum
T2 - The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on P. falciparum
AU - Hatabu, Toshimitsu
AU - Hagiwara, Masaki
AU - Taguchi, Nao
AU - Kiyozawa, Masayuki
AU - Suzuki, Mamoru
AU - Kano, Shigeyuki
AU - Sato, Kumiko
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/3
Y1 - 2006/3
N2 - The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasmodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However, GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy.
AB - The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasmodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However, GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy.
KW - GSH, reduced glutathione
KW - GTX, gliotoxin
KW - Gliotoxin
KW - Plasmodium falciparum
KW - Proteasome inhibitor
KW - RBCs, red blood cells
KW - pRBCs, parasitized red blood cells
UR - http://www.scopus.com/inward/record.url?scp=32644457083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32644457083&partnerID=8YFLogxK
U2 - 10.1016/j.exppara.2005.11.012
DO - 10.1016/j.exppara.2005.11.012
M3 - Article
C2 - 16384554
AN - SCOPUS:32644457083
SN - 0014-4894
VL - 112
SP - 179
EP - 183
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 3
ER -
