INVESTIGADORES
ROMERO jorge Miguel
congresos y reuniones científicas
Título:
GOSPEL enhances in vitro nitric oxide-induced aggregation of GAPDH
Autor/es:
GONZÁLEZ, MARÍA C; INGARAMO, MARÍA C; ROMERO JORGE M; CURTINO JUAN A; CARRIZO, MARÍA E.
Lugar:
Carlos Paz, Córdoba
Reunión:
Congreso; XLII Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2013
Institución organizadora:
Sociedad Argentina de Biofísica (SAB)
Resumen:
Among its
many functions, glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) has a proapoptotic role associated with oxidative and
nitrosative stress. Nitric oxide stress leads to reversible S-nitrosylation of
the active site cysteine of GAPDH. When S-nitrosylated GAPDH binds to the E3-ubiquitin-ligase Siah1 which
possesses a nuclear localization signal that promotes the translocation of the
complex to the nucleus, where both proteins have cytotoxic effects. This
cascade is regulated by S-nitrosylated GOSPEL (GAPDH's competitor Of Siah
Protein Enhances Life) whose association with GAPDH prevents the cytotoxic interaction
GAPDH-Siah1 (1).
Oxidative stress, produced either by hydrogen
peroxide or nitric oxide, can also promote the formation of amyloid-like aggregates of GAPDH through
disulfide bonds involving its active site cysteine (2). It is worth mentioning
that GAPDH has also been found deposited as insoluble aggregates in some
neurodegenerative diseases.
Here we present the analysis of the effect of
GOSPEL on the in vitro aggregation of
GAPDH induced by nitric oxide. Our results indicate that, under these
conditions, both proteins co-aggregate and that the aggregation of GAPDH was
enhanced in the presence of GOSPEL. Our work also includes the characterization
of the aggregates obtained and the study of the nature of the interaction between
the proteins therein.