Gene interactions and pathways from curated databases and text-mining
Stem Cells 2009, PMID: 19544469

Initiation of dopaminergic differentiation of Nurr1(-) mesencephalic precursor cells depends on activation of multiple mitogen-activated protein kinase pathways.

Sabolek, Michael; Baumann, Bernd; Heinrich, Maria; Meyer, Anne K; Herborg, Anna; Liebau, Stefan; Maisel, Martina; Hermann, Andreas; Ventz, Katharina; Schwarz, Johannes; Wirth, Thomas; Storch, Alexander

Interleukin-1 (IL-1) plays a pivotal role in terminal dopaminergic differentiation of midbrain-derived neural precursor cells already committed to the mesencephalic dopaminergic phenotype (named mdNPCs for mesencephalic dopaminergic neural precursor cells). Here we characterized the molecular events in long-term expanded rat nuclear receptor related-1(-) (Nurr1(-)) mdNPCs in response to IL-1beta during their terminal dopaminergic specification. We showed that IL-1beta induced a rapid induction of mRNA of dopaminergic key fate-determining transcription factors, such as Nurr1 and Pitx3, and a subsequent increase of tyrosine hydroxylase protein as an early marker for dopaminergic neurons in vitro. These effects of IL-1beta were specific for mdNPCs and were not observed in striatal neural precursor cells (NPCs). Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta-induced Nurr1 expression and dopaminergic differentiation of mdNPCs. Incubation of mdNPCs with IL-1beta led to a rapid phosphorylation of ERK1/2 and p38 mitogen-activated protein (MAP) kinases within 1 to 3 hours, whereas Jun kinase was not phosphorylated in response to IL-1beta. Consistently, inhibition of the ERK1/2 pathway or p38 MAP kinase blocked Nurr1 upregulation and further dopaminergic specification of mdNPCs, but not differentiation into MAP2ab(+) neurons. IL-1 receptor antagonist did not block early dopaminergic differentiation events, suggesting that the effects of IL-1beta are not mediated through activation of IL-1 receptor type I. Our results indicate that induction of terminal dopaminergic specification of Nurr1(-) mdNPCs by IL-1beta depends on activation of the ERK1/2 and p38 MAP kinase pathway.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

tyrosine hydroxylase → IL-1beta: " We showed that IL-1beta induced a rapid induction of mRNA of dopaminergic key fate determining transcription factors, such as Nurr1 and Pitx3, and a subsequent increase of tyrosine hydroxylase protein as an early marker for dopaminergic neurons in vitro "

NF-kappaB ⊣ transcription factor: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

NF-kappaB ⊣ activating protein 1 (AP-1): " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1) , but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

NF-kappaB ⊣ IL-1beta: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

NF-kappaB ⊣ IL-1beta: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

activating protein 1 (AP-1) → IL-1beta: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1) , but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

activating protein 1 (AP-1) → IL-1beta: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1) , but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

Nurr1 → IL-1beta: " Surprisingly, IL-1beta did not activate the NF-kappaB pathway or the transcription factor activating protein 1 (AP-1), but inhibition of nuclear translocation of NF-kappaB by SN50 facilitated IL-1beta induced Nurr1 expression and dopaminergic differentiation of mdNPCs "

Manually curated Databases

No curated data.