LOCALIZATION AND FUNCTIONAL-ANALYSIS OF THE CYTOSOLIC AND EXTRACELLULAR CUZN SUPEROXIDE DISMUTASES IN THE HUMAN PARASITIC NEMATODE ONCHOCERCA-VOLVULUS

This study describes the histological localization of two CuZn superox ide dismutases (SOD1 and SOD2) in the parasitic nematode Onchocerca vo lvulus. and a functional characterization of the 'extracellular' form of this enzyme (SOD2) which provides evidence that it is involved in t he defense against environmental superoxide anion radicals. These esse ntial enzymes are detected in larval and adult stages of the parasite, determined at the mRNA and protein levels by in situ hybridization an d immunolocalization studies. These proteins are distributed throughou t the worm, at various concentrations with particularly high levels pr oduced in the hypodermis. In vitro maintenance of parasites indicated that SOD2 was secreted outside the parasite into the medium. Baculovir us constructs designed to test the ability of the SOD2 hydrophobic N-t erminal region to function in processing and secretion confirmed the a bility of this polypeptide sequence to direct the secretion of a marke r protein, as well as of the mature SOD2 enzyme. Analyses of the nativ e, mature SOD2 enzyme molecular mass, and the primary and quaternary s tructure, indicate that unlike other extracellular SODs, the SOD2 is a ctive as a non-glycosylated dimer, rather than as a tetrameric glycopr otein. The detection of SOD2 outside of the parasite maintained in vit ro, and the confirmation that the SOD2 is a secreted enzyme, indicate that this enzyme plays a role in the interactive biology of parasitic nematodes with their hosts. (C) 1997 Elsevier Science B.V.