The present address of Dr. N. Llecha is Servei d'Anàlisi Clíniques, Hospital Universitari Arnau de Vilanova, Lleida, Catalonia, Spain.
Extracellular-Regulated Kinases and Phosphatidylinositol 3-Kinase Are Involved in Brain-Derived Neurotrophic Factor-Mediated Survival and neuritogenesis of the Neuroblastoma Cell Line SH-SY5Y
Article first published online: 17 JAN 2002
Journal of Neurochemistry
Volume 73, Issue 4, pages 1409–1421, October 1999
How to Cite
Encinas, M., Iglesias, M., Llecha, N. and Comella, J. X. (1999), Extracellular-Regulated Kinases and Phosphatidylinositol 3-Kinase Are Involved in Brain-Derived Neurotrophic Factor-Mediated Survival and neuritogenesis of the Neuroblastoma Cell Line SH-SY5Y. Journal of Neurochemistry, 73: 1409–1421. doi: 10.1046/j.1471-4159.1999.0731409.x
Abbreviations used : BDNF, brain-derived neurotrophic factor ; DMEM, Dulbecco's modified Eagle's medium ; ERK, extracellular signal-regulated kinase ; GAP-43, growth-associated protein-43 ; MAPK, mitogen-activated protein kinase ; MEK, MAPK and ERK kinase ; NGF, nerve growth factor ; NT-3, neurotrophin-3 ; NT-4/5, neurotrophin-4/5 ; PAGE, polyacrylamide gel electrophoresis ; PBS, phosphate-buffered saline ; PI 3-K, phosphatidylinositol 3-kinase ; PLCγ, phospholipase Cγ ; RA, retinoic acid ; SDS, sodium dodecyl sulfate ; Trk, tropomyosin receptor kinase.
- Issue published online: 17 JAN 2002
- Article first published online: 17 JAN 2002
Abstract : Retinoic acid (RA) induces the differentiation of many cell lines, including those derived from neuroblastoma. RA treatment of SH-SY5Y cells induces the appearance of functional Trk B and Trk C receptors. Acute stimulation of RA-predifferentiated SH-SY5Y cells with brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), or neurotrophin 4/5 (NT-4/5), but not nerve growth factor (NGF), induces Trk autophosphorylation, followed by phosphorylation of Akt and the extracellular signal-regulated kinases (ERKs) 1 and 2. In addition, BDNF, NT-3, or NT-4/5, but not NGF, promotes cell survival and neurite outgrowth in serum-free medium. The mitogen-activated protein kinase and ERK kinase (MEK) inhibitor PD98059 blocks BDNF-induced neurite outgrowth and growth-associated protein-43 expression but has no effects on cell survival. On the other hand, the phosphatidylinositol 3-kinase inhibitor LY249002 reverses the survival response elicited by BDNF, leading to a cell death with morphological features of apoptosis.