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The sialyl transferase, but not the sialidase activity of Trypanosoma cruzi trans-sialidase is involved in the induction of apoptosis
MUCCI JUAN; RISSO MARIKENA; LEGUIZAMÓN M SUSANA; FRASCH A CARLOS; CAMPETELLA OSCAR
Congreso; VII Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2005
Sociedad Argentina de Protozoología y Enfermedades Parasitarias
Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzymatic activity denoted trans-sialidase (TS), amodified sialidase able to transfer sialyl residues among macromolecules. This activity enables the parasite to circumvent its inability to synthesize sialic acid de novo. Sialic acid incorporated through the TS onto the surface molecules is essential for parasite survival in the mammalian host. The enzyme is released from the parasite and therefore, it is able to act far from the infection site inducing apoptosis in cells from the immune system. An unclear question is whether the acquisition or release of sialic acid is associated with apoptosis induction. The administration of lactitol, a preferred substrate for TS was able to prevent the ex vivo as well as the in vivo in crease of apoptotic cell number in the immune system. Pharmacokinetic studies showed that lactitol was able to inhibit the enzyme activity in vitro as well as in vivo. Besides, lactitol inhibited the sialylation reaction, but not the de-sialylation on its respective substrates. Independent support for these findings was provided by lectin histochemistry, which demonstratedthe in vitro sialylation of cell surfaces after enzyme administration. TUNEL labeling increase correlates with the sialyl residue acquisition. Thus, the lesions induced by TS on the immune system are due to the desialylation of natural acceptor molecules. Since the effects of TS can be prevented by lactitol in vivo, the further development of inhibitors of the enzyme might be useful to prevent the damage caused by the parasite.