TGF-beta1 increases tyrosine hydroxylase expression by a mechanism blocked by BMP-2 in human neuroblastoma SH-SY5Y cells.
Human neuroblastoma SH-SY5Y cells were used to study the effects of transforming growth factor beta1 (TGF-beta1) and bone morphogenetic protein 2 (BMP-2) on neuronal differentiation and acquisition of a catecholaminergic phenotype. SH-SY5Y cells express the intracellular factors activated through the receptors of the TGFbeta superfamily members, Smad1 and Smad4, as in basal conditions or after differentiation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or retinoic acid (RA). TGF-beta1 and BMP-2 induce differentiation in SH-SY5Y cells by different pathways: the effect of TGF-beta1 is potentiated by TPA and the effect of BMP-2 is blocked by RA. Cell differentiation due to TGF-beta1 treatment is accompanied by an increase in tyrosine hydroxylase (TH) expression, more pronounced in the presence of TPA or RA and counteracted by BMP-2. BMP-2 and RA both induce noncatecholaminergic cell differentiation, and together they may induce choline acetyltransferase expression in serum-cultured cells. In conclusion, our results suggest that TGF-beta1 and BMP-2 may contribute, in opposite ways, to regulation of the neuronal catecholaminergic phenotype.
Gómez-Santos
Cristina
C
Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, c/Feixa Llarga s/n, E-08907-Hospitalet del Llobregat, Barcelona, Spain.
Ambrosio
Santiago
S
Ventura
Francesc
F
Ferrer
Isidre
I
Reiriz
Julia
J
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D012097:Repressor Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; D051901:Smad4 Protein; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002395:Catecholamines; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; C497399:SMAD1 protein, human; C497796:SMAD4 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D051901:Smad4 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014212:Tretinoin; D014446:Tyrosine 3-Monooxygenase; D010959:Tissue Plasminogen Activator