Artículo

Astort, F.; Repetto, E.M.; Rocha-Viegas, L.; Mercau, M.E.; Sanchez Puch, S.; Finkielstein, C.V.; Pecci, A.; Cymeryng, C.B. "Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway" (2016) Journal of Molecular Endocrinology. 57(2):113-124
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Abstract:

In addition to the well-known function of ACTH as the main regulator of adrenal steroidogenesis, we have previously demonstrated its effect on the transcriptional stimulation of HO-1 expression, a component of the cellular antioxidant defense system. In agreement, we hereby demonstrate that, in adrenocortical Y1 cells, HO-1 induction correlates with a significant prevention of the generation of reactive oxygen species induced by H2O2/Fe2+. ACTH/cAMP-dependent activation of redox-imbalanced related factors such as NRF2 or NFκB and the participation of MAPKs in this mechanism was, however, discarded based on results with specific inhibitors and reporter plasmids. We suggest the involvement of CREB in HO-1 induction by ACTH/cAMP, as transfection of cells with a dominant-negative isoform of CREB (DN-CREB-M1) decreased, while overexpression of CREB increased HO-1 protein levels. Sequence screening of the murine HO-1 promoter revealed CRE-like sites located at −146 and −37 of the transcription start site and ChIP studies indicated that this region recruits phosphorylated CREB (pCREB) upon cAMP stimulation in Y1 cells. In agreement, H89 (PKA inhibitor) or cotransfection with DN-CREB-M1 prevented the 8Br-cAMP-dependent increase in luciferase activity in cells transfected with pHO-1[−295/+74].LUC. ACTH and cAMP treatment induced the activation of the PI3K/Akt signaling pathway in a PKA-independent mechanism. Inhibition of this pathway prevented the cAMP-dependent increase in HO-1 protein levels and luciferase activity in cells transfected with pHO-1[−295/+74].LUC. Finally, here we show a crosstalk between the cAMP/PKA and PI3K pathways that affects the binding of p-CREB to its cognate element in the murine promoter of the Hmox1 gene. © 2016 Society for Endocrinology Printed in Great Britain.

Registro:

Documento: Artículo
Título:Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway
Autor:Astort, F.; Repetto, E.M.; Rocha-Viegas, L.; Mercau, M.E.; Sanchez Puch, S.; Finkielstein, C.V.; Pecci, A.; Cymeryng, C.B.
Filiación:Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IFIBYNE-CONICET, Buenos Aires, Argentina
Integrated Cellular Responses Laboratory, Department of Biological Sciences, Polytechnic Institute and State University, Blacksburg, VA, United States
Palabras clave:Adrenocortical cells; CAMP/PKA; CREB; Heme oxygenase; PI3K; corticotropin; cyclic AMP; cyclic AMP responsive element binding protein; heme oxygenase 1; luciferase; n [2 (4 bromocinnamylamino)ethyl] 5 isoquinolinesulfonamide; phosphatidylinositol 3 kinase; protein kinase B; reactive oxygen metabolite; transcription factor Nrf2; cyclic AMP responsive element binding protein; heme oxygenase 1; phosphatidylinositol 3 kinase; protein binding; reactive oxygen metabolite; adrenal cortex cell; animal cell; Article; controlled study; enzyme activation; enzyme activity; enzyme induction; enzyme inhibition; gene overexpression; mouse; nonhuman; priority journal; promoter region; protein binding; protein phosphorylation; transcription initiation site; transcription regulation; transient transfection; adrenal gland; animal; biological model; cell line; drug effects; gene expression regulation; genetics; metabolism; signal transduction; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Cell Line; Cyclic AMP Response Element-Binding Protein; Gene Expression Regulation; Heme Oxygenase-1; Mice; Models, Biological; Phosphatidylinositol 3-Kinases; Promoter Regions, Genetic; Protein Binding; Reactive Oxygen Species; Signal Transduction
Año:2016
Volumen:57
Número:2
Página de inicio:113
Página de fin:124
DOI: http://dx.doi.org/10.1530/JME-16-0005
Título revista:Journal of Molecular Endocrinology
Título revista abreviado:J. Mol. Endocrinol.
ISSN:09525041
CODEN:JMLEE
CAS:corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; cyclic AMP, 60-92-4; cyclic AMP responsive element binding protein, 130428-87-4, 130939-96-7; n [2 (4 bromocinnamylamino)ethyl] 5 isoquinolinesulfonamide, 127243-85-0; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; Adrenocorticotropic Hormone; Cyclic AMP Response Element-Binding Protein; Heme Oxygenase-1; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09525041_v57_n2_p113_Astort

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Citas:

---------- APA ----------
Astort, F., Repetto, E.M., Rocha-Viegas, L., Mercau, M.E., Sanchez Puch, S., Finkielstein, C.V., Pecci, A.,..., Cymeryng, C.B. (2016) . Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway. Journal of Molecular Endocrinology, 57(2), 113-124.
http://dx.doi.org/10.1530/JME-16-0005
---------- CHICAGO ----------
Astort, F., Repetto, E.M., Rocha-Viegas, L., Mercau, M.E., Sanchez Puch, S., Finkielstein, C.V., et al. "Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway" . Journal of Molecular Endocrinology 57, no. 2 (2016) : 113-124.
http://dx.doi.org/10.1530/JME-16-0005
---------- MLA ----------
Astort, F., Repetto, E.M., Rocha-Viegas, L., Mercau, M.E., Sanchez Puch, S., Finkielstein, C.V., et al. "Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway" . Journal of Molecular Endocrinology, vol. 57, no. 2, 2016, pp. 113-124.
http://dx.doi.org/10.1530/JME-16-0005
---------- VANCOUVER ----------
Astort, F., Repetto, E.M., Rocha-Viegas, L., Mercau, M.E., Sanchez Puch, S., Finkielstein, C.V., et al. Role of CREB on heme oxygenase-1 induction in adrenal cells: Involvement of the PI3K pathway. J. Mol. Endocrinol. 2016;57(2):113-124.
http://dx.doi.org/10.1530/JME-16-0005