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Differential regulation of apoptosis-associated genes by estrogen receptor alpha in human neuroblastoma cells

Article type: Research Article

Authors: Brendel, Alexander | Felzen, Vanessa | Morawe, Tobias | Manthey, Dieter | Behl, Christian

Affiliations: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

Note: [] Both authors contributed equally.

Note: [] Both authors contributed equally.

Note: [] Corresponding author: Christian Behl, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55099 Mainz, Germany. Tel.: +49 6131 39 25890; Fax: +49 6131 39 25792; E-mail: [email protected]

Keywords: Estrogen, ERalpha, neuroprotection, Caspase 3, BAG1, BAG3

DOI: 10.3233/RNN-120272

Journal: Restorative Neurology and Neuroscience, vol. 31, no. 2, pp. 199-211, 2013

Published: 2013
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Abstract

Purpose: The neuroendocrinology of female sex hormones is of great interest for a variety of neuropsychiatric disorders. In fact, estrogens and estrogen receptors (ERs) exert neuromodulatory and neuroprotective functions. Here we investigated potential targets of the ER subtype alpha that may mediate neuroprotection and focused on direct modulators and downstream executors of apoptosis. Methods: We employed subclones of human neuroblastoma cells (SK-N-MC) stably transfected with one of the ER subtypes, ERalpha or ERbeta. Differences between the cell lines regarding the mRNA expression levels were examined by qPCR, changes on protein levels were examined by Western Blot and immunocytochemistry. Differences concerning apoptosis induction were analysed by cell survival assays which included primary rat neurons. Results: In this report we show a potent protection against apoptosis-stimuli in ERalpha expressing cells compared to controls lacking ERalpha. In fact, almost a complete silencing of Caspase 3 expression in SK-ERalpha cells compared to SK-01 control transfected cells was observed. In addition, prosurvival bcl2, bag1 and bag3 expression was highly up-regulated in the presence of ERalpha. Conclusion: Taken together, we identified Caspase 3, BAG1 and BAG3 as key targets of ERalpha in neuronal cells that may play a role in ERalpha-mediated neuroprotection.

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