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23 April 2003

Peroxisomal function is altered during leishmania infection.

Bikramjit Raychaudhury, Shouvik Banerjee, Salil C. Datta

Med Sci Monit 2003; 9(4): BR125-129 :: ID: 4705

Abstract

BACKGROUND: The aim of this study was to investigate host peroxisomal properties after leishmania infection and provide clues to protect peroxisomes during the search for new chemotherapeutic strategies against leishmaniasis. MATERIAL/METHODS: To assess host peroxisomal properties after leishmania infection, we determined catalase, urate oxidase, superoxide dismutase (SOD), dihydroxyacetone phosphate acyl transferase (DHAPAT) and proteinase activities in peroxisomes purified by the nycodenz gradient technique. Spectrophotometric analysis of superoxide radical release and assays of palmitoyl Co-A oxidation were also conducted. SDS-Polyacrylamide gel electrophoresis (SDS-PAGE) and electron microscopy studies were carried out to monitor the status of this microbody after parasite RESULTS: Liver peroxisomes were found to be functionally defective when purified after infection. The activities of catalase, urate oxidase, DHAPAT and SOD were either deficient or could not be detected after parasite infection. H[sub]2[/sub]O[sub]2[/sub] producing peroxisomal ß-oxidation was significantly elevated after 90 days of infection, with concomitant induction of superoxide radical production. Proteolytic activity in infected liver peroxisome was found to be inhibited, pointing to possible uneven processing of peroxisomal proteins. Electron microscopic studies revealed that the morphology of peroxisomes after leishmania infection was impaired. CONCLUSIONS: The evidence obtained for leishmania-induced peroxisomal dysfunction may provide clues to develop new drugs against this parasite, capable of protecting normal function of this ubiquitous host organelle for successful treatment.

Keywords: Leishmania donovani - isolation & purification, Leishmaniasis, Visceral - metabolism, Leishmaniasis, Visceral - pathology, Peroxisomes - enzymology, Peroxisomes - metabolism, Peroxisomes - ultrastructure, Urate Oxidase - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750