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Pouly, S; Storch, MK; Matthieu, JM; Lassmann, H; Monnet-Tschudi, F; Honegger, P.
Demyelination induced by protein kinase C-activating tumor promoters in aggregating brain cell cultures.
J Neurosci Res. 1997; 49(2):121-132 Doi: 10.1002/(SICI)1097-4547(19970715)49:2<121::AID-JNR1>3.0.CO;2-B
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Co-authors Med Uni Graz
Storch Maria
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Abstract:
The plasticity of mature oligodendrocytes was studied in aggregating brain cell cultures at the period of maximal expression of myelin marker proteins. The protein kinase C (PKC)-activating tumor promoters mezerein and phorbol 12-myristate 13-acetate (PMA), but not the inactive phorbol ester analog 4alpha-PMA, caused a pronounced decrease of myelin basic protein (MBP) content and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity. In contrast, myelin/oligodendrocyte protein (MOG) content was affected relatively little. Northern blot analyses showed a rapid reduction of MBP and PLP gene expression induced by mezerein, and both morphological and biochemical findings indicate a drastic loss of compact myelin. During the acute phase of demyelination, only a relatively small increase in cell death was perceptible by in situ end labeling and in situ nick translation. Basic fibroblast growth factor (bFGF) also reduced the levels of the oligodendroglial differentiation markers and enhanced the demyelinating effects of the tumor promoters. The present results suggest that PKC activation resulted in severe demyelination and partial loss of the oligodendrocyte-differentiated phenotype.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Biological Markers - chemistry
Brain - drug effects
Carcinogens - toxicity
Cell Aggregation - drug effects
Cell Differentiation - drug effects
Cells, Cultured - drug effects
Demyelinating Diseases - chemically induced
Diterpenes - chemically induced
Enzyme Activation - chemically induced
Fibroblast Growth Factor 2 - toxicity
Gene Expression - toxicity
Myelin Proteins - genetics
Oligodendroglia - drug effects
Protein Kinase C - metabolism
Rats - metabolism
Terpenes - toxicity
Tetradecanoylphorbol Acetate - toxicity

Find related publications in this database (Keywords)
rat brain
oligodendrocytes
aggregating cell cultures
demyelination
protein kinase C activators
basic fibroblast growth factor
myelin basic protein
2'
'-cyclic nucleotide 3'-phosphohydrolase
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