Abstract
AbsractBackgroundDaidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion (DRG) neuronal cultures, we have examined the potential neurite outgrowth effect of daidzein.MethodsDissociated dorsal root ganglia (DRG) cultures were used to study the signaling mechanism of daidzein-induced neuritogenesis by immunocytochemistry and Western blotting.ResultsIn response to daidzein treatment, DRG neurons showed a significant increase in total neurite length and in tip number per neuron. The neuritogenic effect of daidzein was significantly hampered by specific blockers for Src, protein kinase C delta (PKCδ) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK/ERK), but not by those for estrogen receptor (ER). Moreover, daidzein induced phosphorylation of Src, PKCδ and ERK. The activation of PKCδ by daidzein was attenuated in the presence of a Src kinase inhibitor, and that of ERK by daidzein was diminished in the presence of either a Src or PKCδ inhibitor.ConclusionDaidzein may stimulate neurite outgrowth of DRG neurons depending on Src kinase, PKCδ and ERK signaling pathway.
Highlights
Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system
The neuritogenic effect of daidzein was significantly hampered by specific blockers for Src, protein kinase C delta (PKCδ) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK/Extracellular signal-regulated kinase (ERK)), but not by those for estrogen receptor (ER)
The activation of Protein kinase C subtype delta (PKCδ) by daidzein was attenuated in the presence of a Src kinase inhibitor, and that of ERK by daidzein was diminished in the presence of either a Src or PKCδ inhibitor
Summary
A phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Phytoestrogens are estrogenic compounds of plant origin, and have structures and functions similar to the mammalian endogenous hormone estrogen [3]. Phytoestrogen acts mainly as an ER agonist It may function as an antagonist, by inhibition of aromatase activity in breast cancer cells, and blockage of estrogen uptake by uterine cells [5]. This mixed ER agonist/antagonist property probably explains the potential benefit of phytoestrogen in breast cancer prevention [6,7,8]
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