53 research outputs found
The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor α palmitoylation
Naringenin (Nar) is a component of fruits and vegetables associated
with healthful benefits, such as in osteoporosis, cancer,
and cardiovascular diseases. These protective effects
have been linked with Nar antiestrogenic as well as estrogenic activities. Previous studies indicate that Nar impaired estrogen receptor (ER) alpha signaling by interfering with ERalpha-mediated
activation of ERK and phosphoinositide 3-kinase signaling pathways in the absence of effects at the transcriptional
level. The present studies evaluated the hypothesis that these Nar antagonistic effects occur at the level of the plasma membrane.
Our results indicate that Nar induces ERalpha depalmitoylation
faster than 17beta-estradiol, which results in receptor
rapid dissociation from caveolin-1. Furthermore, Nar impedes ERalpha to bind adaptor (modulator of nongenomic actions of the ER) and signaling (c-Src) proteins involved in the activation of the mitogenic signaling cascades (i.e. ERK and phosphoinositide 3-kinase). On the other hand, Nar induces the ER-dependent,
but palmitoylation-independent, activation of p38
kinase, which in turn is responsible for Nar-mediated antiproliferative
effects in cancer cells. Altogether, these data
highlight new ER-dependent mechanisms on the root of antiproliferative
and antiestrogenic effects of Nar. Moreover,
the different modulation of ERalpha palmitoylation exerted by
different ligands represents a pivotal mechanism that drives cancer cell to proliferation or apoptosis
Estrogen receptor-dependent effects of bisphenol a
Bisphenol A (BPA), commonly used as building block of polycarbonate plastics, significantly affects human and animal health interfering with the action of natural hormones. Within BPA disrupting effects, a mitogenic activity and, consequently, an increased incidence of neoplastic transformations has been reported in exposed organisms. Among the several mechanisms proposed for the mitogenic BPA effects, its ability to bind to estrogen receptors (ERα and ERβ) deserves particular attention. Aim of this work is to investigate ERα- and ERβ-dependent mechanisms underlying BPA proliferative effect. Binding assay confirms that BPA binds to both ERs. Cell vitality assay and Western blot analysis of protein involved in cell proliferation demonstrate that BPA acts as a double side disruptor of estrogenic effects. In fact in the presence of ERα, BPA mimics E2, increasing cell proliferation. On the contrary, in the presence of ERβ, BPA acts as an E2 antagonist preventing the hormone-induced cancer cells apoptosis. These two divergent aspects could act synergistically in the exposed organisms leading to the disruption of the balance between proliferation and apoptosis typical of E2 effects
17β-Estradiol - A new modulator of neuroglobin levels in neurons: Role in neuroprotection against H2O2-induced toxicity
Although discovered in 2000, neuroglobin (Ngb) functions are still uncertain. A contribution to the role played by Ngb in neurons could certainly derive from the identification of Ngb endogenous modulators. Here, we evaluate the possibility that Ngb could be regulated by 17β-estradiol (E 2) signaling in both SK-N-BE human neuroblastoma cell line and mouse hippocampal neurons. 1 nM E2 rapidly induced a 300% increase in Ngb levels in both models. The E2 effect was specific, being not induced by testosterone or dihydrotestosterone. The E2-induced Ngb increase requires estrogen receptor (ER) β, but not ERα, as evaluated by the mimetic effect of ERβ-specific agonist DPN and by the blockage of E 2 effect in ERβ-silenced SK-N-BE cells. Furthermore, both rapid (15 min) ERβ-dependent activation of p38/MAPK and transcriptional ERβ activity were required for the estrogenic regulation of Ngb. Finally, E 2 exerted a protective effect against H2O 2-induced neuroblastoma cell death which was completely prevented in Ngb-silenced cells. Overall, these data suggest that Ngb is part of the E 2 signaling mechanism that is activated to exert protective effects against H2O2-induced neurotoxicity. Copyright © 2011 S. Karger AG, Basel.Peer Reviewe
17beta-Estradiol regulates the first steps of skeletal muscle cell differentiation via ER-alpha-mediated signals
17-Estradiol
(E2) mediates a wide variety of complex biological processes
determining the growth and development of reproductive tract as
well as nonreproductive tissues of male and female individuals. While
E2 effects on the reproductive system, bone, and cardiovascular
system are quite well established, less is known about how it affects
the physiology of other tissues. Skeletal muscle is a tissue that is
expected to be E2 responsive since both isoforms of estrogen receptor
(ER- and ER-) are expressed. Significant sex-related differences
have been described in skeletal muscle, although the role played by E2
and the mechanisms underlying it remain to be determined. Here, we
demonstrate that E2 increases the glucose transporter type 4 translocation
at membranes as well as the expression of well-known differentiation
markers of myogenesis (i.e., myogenin and myosin heavy
chain) in rat myoblast cells (L6). These E2-induced effects require
rapid extranuclear signals and the presence of ER-, whereas no
contribution of IGF-I receptor has been observed. In particular,
ER--dependent Akt activation participates in regulating the first step
of myogenic differentiation. Moreover, both receptors mediate the
E2-induced activation of p38, which, in turn, affects the expression of
myogenin and myosin heavy chain. All together, these data indicate
that E2 should be included in the list of skeletal muscle trophic factors
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