Impact of the estrogen receptor-alpha expression on PC12 cell differentiation and apoptosis. - Université de Rennes Accéder directement au contenu
Communication Dans Un Congrès Année : 2007

Impact of the estrogen receptor-alpha expression on PC12 cell differentiation and apoptosis.

Résumé

Numerous studies, both in vivo and in vitro, have reported neuroprotective and neuronal differentiating actions of estrogens. Most of these estrogenic effects are mediated through specific receptors termed estrogen receptors. The aim of this study was to assess the importance of the estrogen receptor-alpha (ERα) and its different domains in these neuronal processes. We report that unliganded and liganded ERα have profound and distinct effects on neuronal differentiation of PC12 cells by affecting several pathways involved in the nerve growth factor (NGF) signaling. Stably expressed in PC12 cells, the unliganded ER partially inhibits neurite outgrowth induced by NGF. This takes place through a repression of MAPK and PI3K/Akt signaling pathways leading to a negative regulation in the expression of neuronal markers. The repressive action of the unliganded ERα is mediated by its D domain but does not involve transactivation and DNA binding domains of ERα, suggesting that a direct transcriptional activity of ERα is not required. Beside the repressive action, ERα expression in PC12 cells allows an estrogenic potentiation of NGF-induced neurite outgrowth to occur. Such effect can not be ascribed to a release of the inhibition induced by the unliganded ERα since 17βE2 has no effect on NGF-induced activity of the MAPK and Akt signaling pathways. On the other hand, 17βE2 is able to enhance NGF-induced response of VGF and NFLc neuronal markers in ERα PC12 clones. This potentiation is mediated by the transactivation functions of the receptor and its D domain indicating that an ERE-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17βE2 in ERα expressing PC12 cells. Our work demonstrates also that following serum starvation, an estrogen-independent protection against apoptosis occurs in stably transfected PC12 cells expressing ERα. The N-terminal domain which contains transactivation function 1 and the DNA binding domain of ERα are not essential for the antiapoptotic effects of the receptor. In contrast, the D domain and the C-terminal domain are required, which suggests that the protective action of ERα in PC12 cells relies on non-genomic mechanisms. In conclusion, this work demonstrates that ERα expression has a profound impact on the PC12 cell fate and underlines the key role of its D domain in differentiation and apoptosis.
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Dates et versions

hal-00181338 , version 1 (23-10-2007)

Identifiants

  • HAL Id : hal-00181338 , version 1

Citer

François Ferrière, Yohann Mérot, Luc Gailhouste, Guillaume Huet, Frédéric Percevault, et al.. Impact of the estrogen receptor-alpha expression on PC12 cell differentiation and apoptosis.. 11EME journée scientifique du réseau LARC Neurosciences, Oct 2007, Rennes, France. ⟨hal-00181338⟩
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