@entity19316 induces SH-SY5Y cell differentiation toward the neuronal phenotype through activation of the @entity10412 / XXXX / @entity3419 /TopoIIb pathway.

@entity1 @entity19316 @entity14383 @entity16 @entity584 @entity8312 @entity10412 @entity3419 @entity521 @entity1366
UNASSIGNED: @entity19316 ( @entity8312 ) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Previously, we have shown that @entity8312 induces @entity1 SH-SY5Y @entity521 cell differentiation toward the neuronal phenotype by targeting topoisomeraseIIb (TopoIIb), a protein implicated in neural development. In the present study, we aimed to elucidate whether the transcriptional factors @entity3419 ( @entity3419 ) and nuclear factor Y (NF-Y), in addition to the upstream signaling pathways @entity1366 and @entity10412 / @entity584 , are involved in modulating TopoIIb expression in the neuronal differentiation process. We demonstrated that SH-SY5Y cells treated with @entity8312 (80 M) terminally differentiated into neurons, characterized by increased neuronal markers, tubulin bIII and @entity14383 ( @entity14383 ), and increased neurite outgrowth, with no negative effect on cell survival. @entity8312 also increased the expression of TopoIIb, which was accompanied by increased expression of @entity3419 in the differentiated neuron-like cells, whereas NF-Y protein levels remained unchanged following the differentiation progression. We also found that the phosphorylation level of @entity584 , but not @entity1366 , was significantly increased as a result of @entity8312 stimulation. Furthermore, as established by chromatin immunoprecipitation (ChIP) assay, activation of the @entity10412 / @entity584 pathway increased @entity3419 binding to the promoter of the TopoIIb gene. Blockage of @entity10412 / @entity584 was shown to lead to subsequent inhibition of TopoIIb expression and neuronal differentiation. Collectively, the results indicate that the @entity10412 / @entity584 / @entity3419 /TopoIIb signaling pathway is necessary for @entity8312 -induced neuronal differentiation. Our findings offer mechanistic insights into understanding the upstream regulation of TopoIIb in neuronal differentiation, and suggest potential applications of @entity8312 both in neuroscience research and clinical practice to treat relevant @entity16 .
