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Role of Peroxidoxins in Leishmania chagasiSurvival

Authors :
Stephen D. Barr
Lashitew Gedamu
Source :
Journal of Biological Chemistry. 278:10816-10823
Publication Year :
2003
Publisher :
Elsevier BV, 2003.

Abstract

The mechanisms by which Leishmaniaparasites survive exposure to highly reactive oxygen (ROS) and nitrogen (RNS) species within phagosomes of macrophages are not well known. Recently it has been shown that RNS alone is sufficient and necessary to control Leishmania donovani infection in mice (Murray, H. W., and Nathan, C. F. (1999) J. Exp. Med. 189, 741–746). No enzymatic defense against RNS has been discovered inLeishmania to date. We have previously isolated two peroxidoxins (LcPxn1 and LcPxn2) from Leishmania chagasiand showed that recombinant LcPxn1 protein was capable of detoxifying hydrogen peroxide, hydroperoxide, and hydroxyl radicals (Barr, S. D., and Gedamu, L. (2001) J. Biol. Chem. 276, 34279–34287). In further characterizing the physiological role of peroxidoxins in Leishmania survival, we show here that recombinant LcPxn1 protein can detoxify RNS in addition to ROS, whereas recombinant LcPxn2 protein can only detoxify hydrogen peroxide. LcPxn1 and LcPxn2 are localized to the cytoplasm, and overexpression of LcPxn1 in L. chagasi parasites enhanced survival when exposed to exogenous ROS and RNS and enhanced survival within U937 macrophage cells. Site-directed mutagenesis studies revealed that the conserved Cys-52 residue is essential for detoxifying hydrogen peroxide, t-butyl hydroperoxide, and hydroxyl radicals, whereas the conserved Cys-173 residue is essential for detoxifying t-butyl hydroperoxide and peroxynitrite. This is the first report of an enzymatic defense against RNS in Leishmania.

Details

ISSN :
00219258
Volume :
278
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi...........0af82a4b090bd373095ad012970d3a39
Full Text :
https://doi.org/10.1074/jbc.m212990200