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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Myriocin, a Serine Palmitoyltransferase Inhibitor, Blocks Cytokinesis in Leishmania (Viannia) braziliensis Promastigotes

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Author(s):
Castro, Erica V. [1] ; Yoneyama, Kelly G. [1] ; Haapalainen, Edna F. [2] ; Toledo, Marcos S. [1] ; Takahashi, Helio K. [1] ; Straus, Anita H. [1]
Total Authors: 6
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Electron Microscopy Ctr, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Eukaryotic Microbiology; v. 60, n. 4, p. 377-387, JUL 2013.
Web of Science Citations: 5
Abstract

We studied the effect of myriocin, an inhibitor of serine palmitoyltransferase, on cultured Leishmania (Viannia) braziliensis promastigotes. Myriocin significantly reduced synthesis of inositol phosphorylceramide, the major sphingolipid expressed in promastigotes as characterized by thin layer chromatography and electrospray ionization mass spectrometry. Log-phase promastigotes treated with 1M myriocin showed a 52% reduction in growth rate and morphological alterations such as more rounded shape and shorter flagellum. Promastigotes treated with myriocin also displayed a variety of aberrant cell phenotypes. The percentage of cells with one nucleus and one kinetoplast (1N1K), following treatment with 1 or 5M myriocin, decreased from 89% (control value) to 27% or 3%, respectively. The percentage of cells with two nuclei (2N2K) varied from 7% (control value) to 19% and 6% for 1 or 5M myriocin-treated parasites, respectively. High percentage of myriocin-treated parasites exhibited large atypical cells presenting three or more nucleus (32% and 89% for 1 or 5M myriocin, respectively). Transmission electron microscopy following treatment with 1M myriocin showed the presence of 4N parasites possibly as a result of an incomplete cytokinesis. Addition of 3-ketodihidrosphingosine to myriocin-treated promastigotes rescue parasite growth and morphology. Addition of ethanolamine did not rescue the myriocin effect on parasite. Our findings indicate that sphingolipids are essential for the completion of cytokinesis, and may play a major role in cell proliferation in L. (V.) braziliensis, thus, differing from data described for Leishmania major sphingolipid-free mutant, where addition of ethanolamine rescue wild-type parasite characteristics. (AU)

FAPESP's process: 06/07005-4 - Membrane microdomains enriched in (glyco) (sphingo) lipds and sterols: organization, function and cell signaling
Grantee:Helio Kiyoshi Takahashi
Support Opportunities: Research Projects - Thematic Grants