THIOREDOXIN PEROXIDASES FROM BRUGIA-MALAYI

Parasite-derived antioxidant proteins have been implicated in playing an important role in protection against the oxygen radicals that are g enerated during aerobic metabolism and in defense against host immune cell attack. Here we report that filarial nematodes include the thiore doxin peroxidase/thiol-specific antioxidant (TPx/TSA) family of antiox idant proteins as part of their complex defense against radical-mediat ed damage. At the protein level, the TPx/TSA from Brugia malayi (Bm-TP x-1) was approximate to 50% identical and approximate to 60% similar t o TPx/TSAs from mammals, amphibians and yeast. Bm-TPx-1 was also appro ximate to 60% identical to putative TPx proteins from a related filari al nematode, Onchocerca volvulus, and from the free-living nematode Ca enorhabditis elegans. That B. malayi may express multiple forms of mol ecules with TPx/TSA activity was indicated by the identification of a B. malayi gene encoding a second, distinct member of the TPx/TSA famil y (Bm-tpx-2). Bm-tpx-1 was found to be transcribed ih all stages of th e parasite present in the mammalian host and the 25 kDa translation pr oduct was present in all of the developmental stages studied. The resu lts of immunohistochemical, immunofluorescent and immunoprecipitation studies showed Bm-TPx-1 to be localized in the cells of the hypodermis /lateral chord in adult parasites and not to be present at the surface or in excretory/secretory products. The distribution in the parasite suggests that Bm-TPx-1 may play its major role in countering radicals produced within cells. A recombinant form of Bm-TPx-1 was biologically active and capable of protecting DNA from oxygen radical-mediated dam age. Thioredoxin peroxidases may prove to be a critical component in t he parasite's defense against injury caused by oxygen radicals derived from endogenous and exogenous sources. (C) 1998 Elsevier Science B.V. All rights reserved.