Format

Send to

Choose Destination
Mol Cell Endocrinol. 2018 Feb 5;461:64-78. doi: 10.1016/j.mce.2017.08.014. Epub 2017 Aug 30.

Bazedoxifene and raloxifene protect neocortical neurons undergoing hypoxia via targeting ERα and PPAR-γ.

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, Department of Experimental Neuroendocrinology, 31-343 Krakow, Smetna Street 12, Poland.
2
Institute of Pharmacology, Polish Academy of Sciences, Department of Experimental Neuroendocrinology, 31-343 Krakow, Smetna Street 12, Poland. Electronic address: kajta@if-pan.krakow.pl.

Abstract

Selective estrogen receptor modulators (SERMs) such as bazedoxifene and raloxifene are recognized to mainly act via estrogen receptors (ERs), but there is no study examining the involvement of PPAR-γ in their actions, especially in neurons undergoing hypoxia. Little is also known about age-dependent actions of the SERMs on neuronal tissue challenged with hypoxia. In this study, bazedoxifene and raloxifene protected neocortical cells against hypoxia at early and later developmental stages. Both SERMs evoked caspase-3-independent neuroprotection and increased protein levels of ERα (66 and 46 kDa isoforms) and PPAR-γ. In addition, bazedoxifene enhanced expression of ERα-regulated Cyp19a1 mRNA. Using double siRNA silencing, for the first time we demonstrated a key role of ERα and PPAR-γ in the neuroprotective action of the SERMs in neocortical neurons undergoing hypoxia. This study provides prospects for the development of a new therapeutic strategies against hypoxic brain injury that selectively target ERα and/or PPAR-γ.

KEYWORDS:

Bazedoxifene; Estrogen receptors; Hypoxia; Neocortical neurons; Neuroprotection; PPAR-γ; Raloxifene; SERMs

PMID:
28859903
DOI:
10.1016/j.mce.2017.08.014

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center