Linked Life Data

16772336

Source:http://linkedlifedata.com/resource/pubmed/id/16772336

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 13
pubmed:dateCreated
2006-6-21
pubmed:abstractText
Bone-marrow-derived mesenchymal stem cells (MSCs) constitute an interesting cellular source to promote brain regeneration after neurodegenerative diseases. Recently, several studies suggested that oxygen-dependent gene expression is of crucial importance in governing the essential steps of neurogenesis such as cell proliferation, survival and differentiation. In this context, we analysed the effect of the HIF-1 (hypoxia inducible factor-1) activation-mimicking agent CoCl(2) on MSCs. CoCl(2) treatment increased the expression of the anti-proliferative gene BTG2/PC3 and decreased cyclin D1 expression. Expression of HIF-1alpha and its target genes EPO, VEGF and p21 was also upregulated. These changes were followed by inhibition of cell proliferation and morphological changes resulting in neuron-like cells, which had increased neuronal marker expression and responded to neurotransmitters. Echinomycin, a molecule inhibiting HIF-1 DNA-binding activity, blocked the CoCl(2) effect on MSCs. Additionally, by using Y-27632, we demonstrated that Rho kinase (ROCK) inhibition potentiated CoCl(2)-induced MSC differentiation in particular into dopaminergic neuron-like cells as attested by its effect on tyrosine hydroxylase expression. Altogether, these results support the ability of MSCs to differentiate into neuron-like cells in response to CoCl(2), an effect that might act, in part, through HIF-1 activation and cell-cycle arrest, and which is potentiated by inhibition of ROCK.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2667-78
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16772336-Amides, pubmed-meshheading:16772336-Animals, pubmed-meshheading:16772336-Bone Marrow Cells, pubmed-meshheading:16772336-Cell Cycle, pubmed-meshheading:16772336-Cell Differentiation, pubmed-meshheading:16772336-Cell Proliferation, pubmed-meshheading:16772336-Cobalt, pubmed-meshheading:16772336-Down-Regulation, pubmed-meshheading:16772336-Drug Synergism, pubmed-meshheading:16772336-Echinomycin, pubmed-meshheading:16772336-Gene Expression Regulation, pubmed-meshheading:16772336-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:16772336-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16772336-Male, pubmed-meshheading:16772336-Mesenchymal Stem Cells, pubmed-meshheading:16772336-Mice, pubmed-meshheading:16772336-Neurons, pubmed-meshheading:16772336-Protein-Serine-Threonine Kinases, pubmed-meshheading:16772336-Pyridines, pubmed-meshheading:16772336-rho-Associated Kinases
pubmed:year
2006
pubmed:articleTitle
Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells.
pubmed:affiliation
UMR-CNRS 6185, Neurodegenerescence: models and therapeutic strategies, University of Caen, CYCERON, Bd Henri Becquerel, BP 5229, 14074 Caen CEDEX, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't