IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
DIFLUOROMETHYLORNITHINE (DFMO) IS A NEW INHIBITOR OF AUTOPHAGY AND Trypanosoma cruzi INFECTION
Autor/es:
VANRELL MC , CUETO JA , BARCLAY JJ , COLOMBO MI , CARILLO C , GOTTLIEB, RA, ROMANO PS
Lugar:
Mendoza
Reunión:
Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012
Institución organizadora:
Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular
Resumen:
Autophagy is a cell process that in normal conditions serves to
recycle cytoplasmic components and aged or damaged organelles.
The autophagic pathway has been implicated in many physiological
and pathological situations, even during the course of infection by
intracellular pathogens. Recently it was demonstrated that the
polyamine spermidine is a physiological inducer of autophagy.
Otherwise, autophagy induction significantly increases host cell
colonization by , the etiological agent of Chagas disease. In
this work we have analyzed the effect of polyamine depletion on the
autophagic response of the host cell and on infectivity. Our
data show that depleting intracellular polyamines by inhibiting the
biosynthetic enzyme ornithine decarboxylase with DFMO
suppressed the induction of autophagy associated with a decrease in
protein abundance of LC3 and Atg5, two proteins required for
autophagosome formation. As a consequence of inhibiting host cell
autophagy, DFMO impaired colonization, indicating that
polyamines and autophagy facilitate parasite infection. While other
autophagy inhibitors are nonspecific and potentially toxic, DFMO
is an FDAapproved drug that may have value in limiting autophagy
and spread of the infection in Chagas disease and possibly other
pathological settings.