Plasmodium falciparum: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on P. falciparum

Toshimitsu Hatabu, Masaki Hagiwara, Nao Taguchi, Masayuki Kiyozawa, Mamoru Suzuki, Shigeyuki Kano, Kumiko Sato

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)179-183
Number of pages5
JournalExperimental Parasitology
Volume112
Issue number3
DOIs
Publication statusPublished - Mar 1 2006

Keywords

  • GSH, reduced glutathione
  • GTX, gliotoxin
  • Gliotoxin
  • Plasmodium falciparum
  • Proteasome inhibitor
  • RBCs, red blood cells
  • pRBCs, parasitized red blood cells

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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