ROMERO JORGE MIGUEL
Congresos y reuniones científicas
Título:
NO-induced GAPDH aggregation is increased by GOSPEL protein and inhibited by NAD
Autor/es:
GONZÁLEZ, MARÍA C; ROMERO JORGE M; INGARAMO, MARÍA C; CURTINO JUAN A; CARRIZO, MARÍA E.
Lugar:
Mar del Plata
Reunión:
Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2015
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
GOSPEL is the protein reported to compete with Siah1 for binding to GAPDH under S-nitrosylation-induced stress
conditions, thus preventing GAPDH-bound Siah1 nuclear translocation and subsequent apoptosis. It is not known
whether GOSPEL is able to affect the formation of amyloid-like GAPDH aggregates, which also occurs under NO
oxidative stress conditions promoting cell death. Here we report the in vitro enhancement by GOSPEL of the
GAPDH aggregation produced by the NO donor NOR3. The unique cysteine residue of GOSPEL was partially
required for co-aggregation, since the cysteine-free GOSPEL mutant C47S produced a minor aggregation increase.
GOSPEL did not affect the lag time preceding GAPDH aggregation but did accelerate this process once it has begun.
Such acceleration is proposed to occur through its binding to disulfide-bond dimers and low molecular weight
disulfide-crosslinked GAPDH oligomers which act as seed for further protein disulfide-interlink and insoluble
aggregate formation. Both GAPDH aggregation and co-aggregation with GOSPEL were inhibited by NAD, a
heretofore not described protective effect of this coenzyme against the damaging consequences of oxidative stress.
This is the first report on GOSPEL favoring the oxidized GAPDH aggregation involved in cell death, in opposite way
to the helpful effect against the apoptotic nuclear translocation of the glycolytic enzyme
conditions, thus preventing GAPDH-bound Siah1 nuclear translocation and subsequent apoptosis. It is not known
whether GOSPEL is able to affect the formation of amyloid-like GAPDH aggregates, which also occurs under NO
oxidative stress conditions promoting cell death. Here we report the in vitro enhancement by GOSPEL of the
GAPDH aggregation produced by the NO donor NOR3. The unique cysteine residue of GOSPEL was partially
required for co-aggregation, since the cysteine-free GOSPEL mutant C47S produced a minor aggregation increase.
GOSPEL did not affect the lag time preceding GAPDH aggregation but did accelerate this process once it has begun.
Such acceleration is proposed to occur through its binding to disulfide-bond dimers and low molecular weight
disulfide-crosslinked GAPDH oligomers which act as seed for further protein disulfide-interlink and insoluble
aggregate formation. Both GAPDH aggregation and co-aggregation with GOSPEL were inhibited by NAD, a
heretofore not described protective effect of this coenzyme against the damaging consequences of oxidative stress.
This is the first report on GOSPEL favoring the oxidized GAPDH aggregation involved in cell death, in opposite way
to the helpful effect against the apoptotic nuclear translocation of the glycolytic enzyme
