Activation of NF-kB transcription factor is involved in the inhibition of cardiomyocytes apoptosis following Trypanosoma cruzi infection or cruzipain treatment.

AOKI, MARIA DEL PILAR; PELLEGRINI, ANDREA; CANO, ROXANA; TANOS, TAMARA, COSO, OMAR; GUIÑAZÚ, NATALIA; GEA, SUSANA.

Rosario

Jornada; Reunion de la Sociedad Argentina de Protozoologia; 2004

Sociedad Argentina de Protozoologia

 

*Dpto. de Bioquímica Clínica. CIBICI-CONICET. Fac. Cs. Qcas. UNC.  paoki@bioclin.fcq.unc.edu.ar. § LFBM. Fac. Cs. Exactas y Naturales. UBA.

Recently, we demonstrated that neonatal cardiomyocyte cultures infected with T. cruzi and subjected to serum starvation displayed a parasite dose-dependent increase in cell viability. Cruzipain (Cz) treatment also reproduces the antiapoptotic effect of the parasites through activation of ERK 1,2-MAPK and PI-3K/AkT but not p38-MAPK signaling pathways .

The aim of the present work was to study the involvement of NF-kB in the cardioprotective effect of Cz. Cardiomyocytes from neonatal BALB/c mice were cultured in DMEM-0,1% FBS and then stimulated with 10 ug/ml of Cz or with Cz + 2,5 mM sulfosalazine (NF-kB inhibitor) for 24h or maintained in medium alone as control. The cell viability percentages determined by Trypan Blue exclusion staining were: 56±2% (control), 85±2% (Cz), 44±9% (Cz+inh). Apoptotic cell death rates assessed by flow cytometry were: 24±4%; 13±4% and 28±4% respectively. The activation of NF-kB was confirmed by immunofluorescence using an anti-p65 polyclonal antibody: Nuclear translocation was examined at 40 min after stimulation: 5±2% (control), 36±5% (Cz), 6±2% (Cz+inh) and 14±5% (infected with T. cruzi).

We conclude that activation of NF-KB transcription factor is required for the antiapoptotic effect of Cz on cardiomyocytes.

This proyect was supported by Fundación Antorchas, Banco Nación and FONCyT,