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Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Retinoic Acid Is Required for Neural Differentiation of SH-SY5Y Human Neuroblastoma Cells
Open accessAbstract
Retinoic acid (RA) induces neural differentiation of SH-SY5Y neuroblastoma cells. We show that the mRNA levels of the differentiation-inhibiting basic helix-loop-helix transcription factors ID1, ID2, and ID3 are down-regulated during RA-induced differentiation of SH-SY5Y cells. The levels of ID proteins decreased in parallel to the observed transcriptional repression. The expression of other basic helix-loop-helix genes changed during RA-induced differentiation: expression of neuroblast-specific ASCL1 (HASH-1) gene was promptly reduced after RA treatment, whereas expression of differentiation-promoting genes NEUROD6 (NEX-1, HATH-2) and NEUROD1 was increased. Treatments with 12-O-tetradecanoylphorbol-13-acetate, another inducer of neuroblastoma cell differentiation, also resulted in coordinated down-regulation of ID gene expression, underscoring the role of ID genes in differentiation. Down-regulation of ID gene expression by RA involves a complex mechanism because full transcriptional repression required newly synthesized proteins and signaling by phosphatidylinositol 3-kinase (PI3K). RA treatment activates the PI3K/Akt signaling pathway, resulting in increased PI3K activity in extracts from RA-treated cells and a rapid increase in phosphorylation of Akt in Ser-473. Inhibition of PI3K by LY294002 impaired RA-induced differentiation, as assessed by morphological and biochemical criteria. We propose that RA, by activating the PI3K/Akt signaling pathway, plays an important role in the regulation of neuronal cell survival.
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Cited by
Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology
Kovalevich, J., & Langford, D. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-640-5_2 · Cited by 1,005
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Self-citationVitamin A and the regulation of fat reserves
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Metadata
- Authors
- López-Carballo, G., Moreno, L., Masiá, S., Pérez, P., & Barettino, D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 277
- Issue
- 28
- Pages
- 25297-25304
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2007466152
- Cited by
- 301
- References
- 71
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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