Autor: |
Rayane Souza, Monara Vieira de Castro, Carlos Artério Sorgi, Jonilson Berlink Lima, Lúcia Helena Faccioli, Victor De Souza Tavares, Yasmin Monara Ferreira de Sousa Andrade, Théo Araújo-Santos, Valeria Borges |
Rok vydání: |
2022 |
Předmět: |
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DOI: |
10.1101/2022.07.01.498279 |
Popis: |
Leishmania parasites contain lipid droplets (LD, or lipid bodies) and the molecular machinery responsible for synthesizing prostaglandins (PGs) and other bioactive lipids. We studied the effects of polyunsaturated fatty acids (PUFA) on LD biogenesis and eicosanoid production in distinct Leishmania species associated with different clinical forms of leishmaniasis. We also compared structural models of human-like cyclooxygenase-2 (GP63) and prostaglandin F synthase (PGFS) proteins of Leishmania, and we evaluated their enzymatic production in logarithmic and stationary growth phases of procyclic L. amazonensis, L. braziliensis and L. infantum. PUFAs modulate the formation of LDs in L. braziliensis and L. infantum. Leishmania species with equivalent clinical manifestations and tissue tropism had same protein mutations in GP63 and PGFS. No differences in GP63 production were observed among L. amazonensis, L. braziliensis and L. infantum, however increased PGFS production was detected during the parasite differentiation. Stimulation with arachidonic acid resulted in highly elevated production of hydroxyeicosatetraenoic acids compared to prostaglandins quantified by LC-MS/MS. The present findings open new perspectives on the role of eicosanoid metabolism in Leishmania and could contribute to the development of novel antiparasitic drugs. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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