Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hanada, K. Articles by Mitamura, T. Search for Related Content PubMed Articles by Hanada, K. Articles by Mitamura, T. Social Bookmarking                      What's this?

¹ Department of Biochemistry and Cell Biology, Japan Science and Technology Corporation, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
² CREST, Japan Science and Technology Corporation, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
³ Department of Molecular Protozoology, Research Institute for Microbial Diseases
⁴ Genome Information Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

Address correspondence to Toshihide Mitamura, Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. Phone: 81-6-6879-8279; Fax: 81-6-6879-8281; E-mail: mitamura{at}biken.osaka-u.ac.jp, and Kentaro Hanada, Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111 (ext. 2126); Fax: 81-3-5285-1157; E-mail: hanak{at}nih.go.jp

Sphingomyelinase (SMase) is one of the principal enzymes in sphingomyelin (SM) metabolism. Here, we identified a Plasmodium falciparum gene (PfNSM) encoding a 46-kD protein, the amino acid sequence of which is 25% identical to that of bacteria SMases. Biochemical analyses of the recombinant protein GST-PfNSM, a fusion protein of the PfNSM product with glutathione-S-transferase, reveal that this enzyme retained similar characteristics in various aspects to SMase detected in P. falciparum–infected erythrocytes and isolated parasites. In addition, the recombinant protein retains hydrolyzing activity not only of SM but also of lysocholinephospholipids (LCPL) including lysophosphatidylcholine and lysoplatelet-activating factor, indicating that PfNSM encodes SM/LCPL-phospholipase C (PLC). Scyphostatin inhibited SM/LCPL-PLC activities of the PfNSM product as well as the intraerythrocytic proliferation of P. falciparum in a dose-dependent manner with ID₅₀ values for SM/LCPL-PLC activities and the parasite growth at 3–5 µM and 7 µM, respectively. Morphological analysis demonstrated most severe impairment in the intraerythrocytic development with the addition of scyphostatin at trophozoite stage than at ring or schizont stages, suggesting its effect specifically on the stage progression from trophozoite to schizont, coinciding with the active transcription of PfNSM gene.

Key Words: lysophosphatidylcholine • lysoplatelet-activating factor • sphingosylphosphocholine • sphingomyelinase • intraerythrocytic stage

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Aoki, S., Li, J., Itagaki, S., Okech, B. A., Egwang, T. G., Matsuoka, H., Palacpac, N. M. Q., Mitamura, T., Horii, T. (2002). Serine Repeat Antigen (SERA5) Is Predominantly Expressed among the SERA Multigene Family of Plasmodium falciparum, and the Acquired Antibody Titers Correlate with Serum Inhibition of the Parasite Growth. J. Biol. Chem. 277: 47533-47540 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS