Document Detail

Neurotrophic actions of PACAP-38 and LIF on human neuroblastoma SH-SY5Y cells.
MedLine Citation:
PMID:  18506635     Owner:  NLM     Status:  MEDLINE    
The neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and leukemia inhibitory factor (LIF) were investigated in human neuroblastoma SH-SY5Y cells. Effects on differentiation were assessed through monitoring morphological changes and Western blot analysis of the expression of neuronal marker proteins. In contrast to PACAP-38, which induced a 5.5-fold increase in the number of neurite-bearing cells, LIF had no significant effect on cell morphology compared to control cells over the 4-day time course. Cells co-treated with PACAP-38+LIF showed a similar increase in neurite-bearing cells compared to those treated with PACAP-38 alone. Cell morphology was similar for PACAP-38-treated and PACAP-38+LIF-co-treated cells, with the formation of bipolar neuron-like cells with long thin neurites, topped by growth cone-like structures and varicosities. SH-SY5Y cells express tyrosine hydroxylase (TH) but only low levels of the neuronal marker proteins: Bcl-2, GAP-43 and choline acetyltransferase (ChAT). Treatment of cells with PACAP-38 induced the expression of Bcl-2, GAP-43, and ChAT but did not appear to alter the expression of TH. LIF failed to induce the expression of GAP-43 and had little effect on the expression of TH, but did induce the expression of Bcl-2 and upregulated the expression of ChAT. Co-treatment with LIF had no effect on PACAP-38-induced expression of Bcl-2, GAP-43, and ChAT. Cells differentiated for 4 days with PACAP-38 or treated with LIF also displayed increased resistance to hypoxic conditions and to treatment with H2O2 and TNFalpha. The increased resistance to hypoxic conditions for PACAP-differentiated cells was blocked by the p38 MAP kinase inhibitor, SB203580, but not by the MEK1 inhibitor, PD98059. Additionally, cell proliferation assays show that LIF, but not PACAP-38, stimulates proliferation of SH-SY5Y cells, and this observed increase by LIF is not attenuated by co-treatment with PACAP. Further investigation of the intracellular signaling pathways mediating the neurotrophic effects of PACAP on SH-SY5Y cells indicate that neither phospholipase C activation nor Ca2+/calmodulin-dependent kinase II (CAMKII) are involved.
T K Monaghan; C Pou; C J MacKenzie; R Plevin; E M Lutz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-28
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  36     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-26     Completed Date:  2009-02-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  45-56     Citation Subset:  IM    
Strathclyde Institute of Pharmacy and Biomedical Sciences, Royal College, 204 George Street, Glasgow, G1 1XW, UK.
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MeSH Terms
Biological Markers / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cell Differentiation / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Shape
Leukemia Inhibitory Factor / pharmacology*
Nerve Growth Factors / pharmacology*
Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*
Receptors, OSM-LIF / genetics,  metabolism
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics,  metabolism
Type C Phospholipases / metabolism
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Biological Markers; 0/LIF protein, human; 0/Leukemia Inhibitory Factor; 0/Nerve Growth Factors; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/Receptors, OSM-LIF; 0/Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; EC Protein Kinase Type 2; EC 3.1.4.-/Type C Phospholipases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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