| Title | Neurosteroids and new synthetic analogs protect sympathoadrenal cells against apoptosis, regulating multiple prosurvival factors | |
| Author | G. Charalampopoulos1, C. Tsatsanis2, I. Alexaki3, N. Avlonitis4, E. Polakis1, T. Calogeropoulou4, E. Castanas3, A. N. Margioris2, and A. Gravanis1.
Departments of Pharmacology1, Clinical Chemistry2, and Experimental Endocrinology3, School of Medicine, University of Crete, Heraklion 71110, and Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation4, Athens |
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| Citation | Charalampopoulos, I., Tsatsanis, C., Alexaki, I. Avlonitis, N., Polakis, E., et al.: Neurosteroids and new synthetic analogs protect sympathoadrenal cells against apoptosis, regulating multiple prosurvival factors, Epitheorese Klin. Farmakol. Farmakokinet. 18(1): 55-58 (2004) | |
| Publication Date | Accepted for publication: 2004 | |
| Full Text Language | English | |
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| Keywords | Ischemia, Dehydroepiandrosterone, Allopregnanolone, Bcl-2, proteins | |
| Other Terms | review article | |
| Summary | Dehydroepiandrosterone and its sulfate ester are mainly produced in human adrenal cortex and in various CNS sites. Recent findings suggest that Dehydroepiandrosterone(S) protects hippocampal and cortical neurons from various insults, including ischemia and excitotoxicity. In the present study we provide evidence that Dehydroepi-androsterone(S) and Allopregnanolone may prevent apoptosis of sympathoadrenal medulla cells, adjacent to their primary site of production in adrenals. Their cytoprotective effects are mediated via the antiapoptotic Bcl-2 proteins and the up-stream regulators of Bcl-2 gene expression and phosphorylation/activation, i.e. transcription factors CREB and NF-KB and kinase PKCa/β. Additionally, synthetic allopregnanolone analogs, deprived of endocrine actions, show strong cytoprotective, antiapoptotic effects on sympathoadrenal cells. | |
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2. Compagnone N.A., Mellon S.H.: Neurosteroids: biosynthesis and function of these novel neuromodulators. Front. Neuroendocrinol. 21: 1-56 (2000) 3. Riccio A., Ahn S., Davenport C.M., Blendy J.A., Ginty D.D.: Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science 286. 2358-2361 (1999) 4. Tamatani M., Che Y.O., Matsuzaki H., Ogawa S., Okado G., Miyake S.H., Mizuno T., Tohyama M.: Tumor necrosis factor induces Bc!-2 and Bcl-x expression through NFkB activation in primary hippocampal neurons. J. Biol. Chem. 274: 8531-8538 (1999) 5. Ruvolo P., Deng X., Carr B., May W.S.: A functional role for protein kinase Cot in Bcl2 phosphorylation and suppression of apoptosis. J. Biol. Chem. 273: 25436-25442 (1998) 6. Dermitzaki E., Tsatsanis C., Gravanis A., Margioris A.: Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC 12 cells via activation of p38 mitogen-activated protein kinase. J. Biol. Chem. 277: 12280-12287 (2002) |
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| Relative Papers |
Online ISSN 1011-6575
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