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| Author(s): |
Cristiana de Melo Trinconi
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2011-09-26 |
| Examining board members: |
Silvia Reni Bortolin Uliana;
Norton Heise;
Carlos Eduardo Winter
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| Advisor: | Silvia Reni Bortolin Uliana |
| Abstract | |
Leishmaniasis is a widely distributed parasitic disease with difficult treatment. The leishmanicidal activity of tamoxifen was recently identified, leading to its proposal as an alternative treatment for leishmaniasis. In this work, we aimed at characterizing the activity of ceramide synthase (CerS) in L. amazonensis and testing whether this enzymatic activity in inhibited by tamoxifen. We have identified, in the L. amazonensis genome, an ORF which encodes a protein similar to the Saccharomyces cerevisiae CerS, with six transmembrane domains and a characteristic Lag1 motif. The characterization of the in vitro enzymatic activity showed that the enzyme recognizes sphingosine/sphinganine as well as palmitoyl/miristoyl CoA as precursors. This enzyme is not sensitive to fumonisin B2 or tamoxifen. This indicates that this drug does not act through the inibition of CerS. The complete characterization of this enzyme will provide valuable information about the sphingolipid methabolism of these protozoa. (AU) | |
| FAPESP's process: | 09/04475-8 - MOLECULAR AND FUNCTIONAL CHARACTERIZATION OF Leishmania amazonensis CERAMIDE SYNTHASE GENE AND INVESTIGATION OF TAMOXIFEN INTERFERENCE ON CERAMIDE BIOSYNTHESIS IN Leishmania |
| Grantee: | Cristiana de Melo Trinconi Tronco |
| Support Opportunities: | Scholarships in Brazil - Master |