IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CREB MEDIATES ACTH DEPENDENT HO-1 EXPRESSION IN ADRENAL CELLS: ROLE OF PI3K PATHWAY
Autor/es:
CYMERYNG CB; MERCAU ME; REPETTO EM; VECINO C; CALDARERI L; ROCHA-VIEGAS L; PECCI A; ASTORT F
Lugar:
Bariloche
Reunión:
Congreso; 3rd South American Symposium in Signal Transduction and Molecular Medicine; 2015
Institución organizadora:
SISTAM
Resumen:
Stimulation of adrenal steroidogenesis by ACTH has been associated with increased generation of reactive oxygen species. Accordingly, we have previously shown that induction of HO-1 by ACTH in adrenocortical cells prevent deleterious effects caused by oxidative stress. We have also demonstrated that HO-1-induction by ACTH involves transcriptional effects and activation of the cAMP/PKA pathway. In the present study we followed a sequential deletion protocol to localize the promoter region of the mouse HO-1 gene involved in the induction of HO-1 by ACTH/cAMP in adrenocortical cells. By using luciferase reporter constructs with pharmacological inhibitors (H89) or dominant negative CREB isoforms we identified a regulatory region located within the proximal promoter (-295/+74), involved in the transcriptional stimulation of HO-1. Sequence analysis indicates that this region includes two putative cAMP-responsive elements (CRE). We also demonstrate the involvement of PI3K/Akt pathway in the induction of HO-1 by ACTH/cAMP. Finally we showed that stimulation of the ACTH/cAMP pathway induces the recruitment of the phosphorylated CRE-binding protein (pCREB) to the promoter region of the endogenous HO-1 gene and demonstrated that this mechanism is also modulated by the activation of the PI3K pathway. In summary, in this study we identified a region in the proximal promoter of the HO-1 gene, containing putative CRE sites, that is involved in its transcriptional stimulation by ACTH. We showed that both cAMP and PI3K pathways are involved in this mechanism and that a crosstalk is established.