Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi

Hydroperoxide metabolism in Crithidia fasciculata has recently been shown t o be catalyzed by a cascade of three oxidoreductases comprising trypanothio ne reductase (TR), tryparedoxin (TXN1), and tryparedoxin peroxidase (TXNPx) (Nogoceke et al., Biol. Chem. 378, 827-836, 1997). The existence of this m etabolic system in the human pathogen Trypanosoma cruzi is supported here b y immunohistochemistry. Epimastigotes of T. cruzi display strong immunoreac tivity with antibodies raised against TXN1 and TXNPx of C. fasciculata. In addition, a full-length open reading frame presumed to encode a peroxiredox in-type protein in T. cruzi (Acc. Nr. AJ 012101) was heterologously express ed in Escherichia coli and shown to exhibit tryparedoxin peroxidase activit y. With TXN, TXNPx, trypanothione and TR, T. cruzi possesses all components constituting the crithidial peroxidase system. It is concluded that the an tioxidant defense of T. cruzi also depends on the NADPH-fuelled, trypanothi one-mediated enzymatic hydroperoxide metabolism. (C) 2000 Elsevier Science Inc.