CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Nitric oxide induces HO-1 in adrenocortical cells
Autor/es:
ASTORT, FRANCISCO; MERCAU, MARIA ELISA; MARTINEZ CALEJMAN, CAMILA; REPETTO, ESTEBAN M.; ARIAS, PABLO; CYMERYNG, CORA BEATRIZ
Lugar:
Los Cocos, Cordoba
Reunión:
Simposio; Spring symposium on Signal Transduction; 2010
Resumen:
Previous
results from our laboratory demonstrated the reciprocal regulation of two local
modulatory systems of adrenal steroidogenesis, e.g. nitric oxide (NO) synthase
and heme oxygenase (HO). We then showed that adrenal HO-1 expression levels
were positively regulated by endogenously generated NO. Present experiments
were designed to analyze the mechanisms involved in the induction of HO-1 by NO
in adrenal cells.
Both HO-1 mRNA and protein levels were
upregulated in Y1 cells incubated for 8 hours in the presence of a NO donor
(DETA-NO, 1 mM).
The signalling pathways involved were then
analyzed. In regard to the NFkB pathway, DETA-NO treatment resulted in a significant
inhibition of the activity of the reporter plasmid KB-LUC, while overexpression
of p65 decreased HO-1 protein levels. At the same time, DETA-NO had no
significant effect on the activity of a Nrf2 reporter plasmid although Nrf2
overexpression significantly increased HO-1 protein levels. PKC inhibition
blocked the increase in HO-1 protein levels triggered by the NO-donor.
We hypothesize that in Y1 adrenal
cells the NO-induced increase in HO-1 expression levels is negatively regulated
by NFkB-dependent mechanisms,
is independent of the activation of the redox dependent transcription factor
Nrf2, and is mediated by a PKC-dependent mechanism. The possible involvement of
a NO-dependent HO-1 mRNA stabilization mechanism is currently under
investigation.