Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi.
Hydroperoxide metabolism in Crithidia fasciculata has recently been shown to be catalyzed by a cascade of three oxidoreductases comprising trypanothione reductase (TR), tryparedoxin (TXN1), and tryparedoxin peroxidase (TXNPx) (Nogoceke et al., Biol. Chem. 378, 827-836, 1997). The existence of this metabolic system in the human pathogen Trypanosoma cruzi is supported here by immunohistochemistry. Epimastigotes of T. cruzi display strong immunoreactivity with antibodies raised against TXN1 and TXNPx of C. fasciculata. In addition, a full-length open reading frame presumed to encode a peroxiredoxin-type protein in T. cruzi (Acc. Nr. AJ 012101) was heterologously expressed in Escherichia coli and shown to exhibit tryparedoxin peroxidase activity. With TXN, TXNPx, trypanothione and TR, T. cruzi possesses all components constituting the crithidial peroxidase system. It is concluded that the antioxidant defense of T. cruzi also depends on the NADPH-fuelled, trypanothione-mediated enzymatic hydroperoxide metabolism.
Lopez
J A
JA
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Carvalho
T U
TU
de Souza
W
W
Flohé
L
L
Guerrero
S A
SA
Montemartini
M
M
Kalisz
H M
HM
Nogoceke
E
E
Singh
M
M
Alves
M J
MJ
Colli
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression; D017125:Genes, Protozoan; D006801:Humans; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D005609:Free Radicals; D015800:Protozoan Proteins; C114110:tryparedoxin; D013879:Thioredoxins; D009249:NADP; D010544:Peroxidases; C119445:trypanothione peroxidase; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase