Autor: |
Bishop, Tammie
Gallagher, Denis Pascual Bravo, Alberto Lygate, Craig A. Bono, Joseph P. de Nicholls, Lynn G. Ortega Sáenz, Patricia Oster, Henrik Wijeyekoon, Bhathiya Sutherland, Andrew I. Grosfeld, Alexandra Aragones, Julian Schneider, Martin Geyte, Katie van Teixeira, Dania Diez Juan, Antonio López Barneo, José Channon, Keith M. Maxwell, Patrick H. Pugh, Christopher W. Davies, Alun M. Carmeliet, Peter Ratcliffe, Peter J. |
Departamento: | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha: | 2008 |
Publicado en: | Molecular and Cellular Biology, 28 (10), 3386-400. |
Tipo de documento: | Artículo |
Resumen: |
Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3_/_ mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3_/_ mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3_/_ mice with HIF-1a_/_ and HIF-2a_/_ mice demonstrated an interaction with HIF-2_ but not HIF-1_, supporting the nonredundant involvement of a PHD3–HIF-2_ pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3_/_ mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the... [Ver más] |
URI: http://hdl.handle.net/11441/17802
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