論文

査読有り
2012年7月

Blockage of Spontaneous Ca2+ Oscillation Causes Cell Death in Intraerythrocitic Plasmodium falciparum

PLOS ONE
  • Masahiro Enomoto
  • ,
  • Shin-ichiro Kawazu
  • ,
  • Satoru Kawai
  • ,
  • Wakako Furuyama
  • ,
  • Tohru Ikegami
  • ,
  • Jun-ichi Watanabe
  • ,
  • Katsuhiko Mikoshiba

7
7
開始ページ
e39499
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0039499
出版者・発行元
PUBLIC LIBRARY SCIENCE

Malaria remains one of the world's most important infectious diseases and is responsible for enormous mortality and morbidity. Resistance to antimalarial drugs is a challenging problem in malaria control. Clinical malaria is associated with the proliferation and development of Plasmodium parasites in human erythrocytes. Especially, the development into the mature forms (trophozoite and schizont) of Plasmodium falciparum (P. falciparum) causes severe malaria symptoms due to a distinctive property, sequestration which is not shared by any other human malaria. Ca2+ is well known to be a highly versatile intracellular messenger that regulates many different cellular processes. Cytosolic Ca2+ increases evoked by extracellular stimuli are often observed in the form of oscillating Ca2+ spikes (Ca2+ oscillation) in eukaryotic cells. However, in lower eukaryotic and plant cells the physiological roles and the molecular mechanisms of Ca2+ oscillation are poorly understood. Here, we showed the observation of the inositol 1,4,5-trisphospate (IP3)-dependent spontaneous Ca2+ oscillation in P. falciparum without any exogenous extracellular stimulation by using live cell fluorescence Ca2+ imaging. Intraerythrocytic P. falciparum exhibited stage-specific Ca2+ oscillations in ring form and trophozoite stages which were blocked by IP3 receptor inhibitor, 2-aminoethyl diphenylborinate (2-APB). Analyses of parasitaemia and parasite size and electron micrograph of 2-APB-treated P. falciparum revealed that 2-APB severely obstructed the intraerythrocytic maturation, resulting in cell death of the parasites. Furthermore, we confirmed the similar lethal effect of 2-APB on the chloroquine-resistant strain of P. falciparum. To our best knowledge, we for the first time showed the existence of the spontaneous Ca2+ oscillation in Plasmodium species and clearly demonstrated that IP3-dependent spontaneous Ca2+ oscillation in P. falciparum is critical for the development of the blood stage of the parasites. Our results provide a novel concept that IP3/Ca2+ signaling pathway in the intraerythrocytic malaria parasites is a promising target for antimalarial drug development.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0039499
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22792177
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000306461800014&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0039499
  • ISSN : 1932-6203
  • PubMed ID : 22792177
  • Web of Science ID : WOS:000306461800014

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