INVESTIGADORES
PREGI Nicolas
congresos y reuniones científicas
Título:
Oxidative stress induces activation of the transcription factor CREB in neuronal cell.
Autor/es:
PREGI, N; BYK, L; MARAZITA, M; CÁNEPA, ET
Lugar:
Villa Carlos Paz, Córdoba, Argentina
Reunión:
Congreso; XLIV Reunión Científica Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
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OXIDATIVE STRESS INDUCES
ACTIVATION OF THE
TRANSCRIPTION FACTOR CREB IN
NEURONAL CELLS
Pregi N, Byk L, Marazita MC, Cánepa ET.
Laboratorio de Biología Molecular - Departamento de
Química
Biológica FCEN UBA Buenos Aires. E-mail:
npregi@qb.fcen.uba.ar
Cyclic AMP response element binding
(CREB) protein, a
transcription factor, mediates responses
to a number of
physiological and pathological signals
such as neurotransmitters,
mitogens, and stress factors.
Phosphorylation of CREB at Ser133, a
well-characterized modification site,
seems to be necessary but not
sufficient to trigger its activation,
suggesting a requirement for
additional independent mechanisms
including other
phosphorylation sites and pathways. The
aim of this work is to study
the role of CREB in the DNA damage
response in neuronal cells. In
particular, the modification of CREB at
phosphorylation sites in
addition to Ser133 will be
explored. Metabolic labeling of cells with
32P-ATP followed by treatment with H2O2 showed
that CREB
becomes phosphorylated starting at 30
minutes post-treatment.
However, unlike treatment with cAMP,
addition of H2O2 did not
induce phosphorylation of CREB at Ser133,
as detected by Western
blot. H2O2 also
activated CREB transcriptional activity 3.5-fold in
reporter assays using p4xCRE-CAT. This
effect was partially
blocked by inhibitors of Ras (PD152440)
and MEK (PD98059)
indicating that the Ras/ERK pathway is
involved in the activation of
CREB by H2O2.
Taken together, these results suggest that H2O2
activates CREB by phosphorylation at
sites other than the canonical
Ser133 through a
pathway that requires Ras and MEK activity.