Chemical inhibitors of cyclin-dependent kinases control proliferation, apoptosis and differentiation of oligodendroglial cells.
Since cyclin-dependent kinases (Cdks) and their endogenous inhibitors (Cdkis) play an essential role as regulators of cell cycle withdrawal and onset of differentiation within oligodendroglial cells, we assessed here the effects of exogenous chemical Cdk inhibitors (CKIs) on cultured rat cortical oligodendrocyte progenitor cells (OPCs). We showed that purine derivatives and especially roscovitine strongly inhibited OPCs proliferation. In the presence of mitogenic signals, roscovitine synergized with thyroid hormone to stimulate oligodendrocyte differentiation. Roscovitine also prevented oligodendroglial apoptosis induced by growth factor deprivation. We thus demonstrated that small molecular weight chemical CKIs have important effects on crucial events of oligodendroglial development in vitro. This might open prospects for using these apparently well tolerated agents in remyelination strategies.
Nguyen
Laurent
L
Center for Cellular and Molecular Neurobiology, University of Liège, 17 Place Delcour, B-4020 Liège, Belgium.
Malgrange
Brigitte
B
Rocher
Véronique
V
Hans
Grégory
G
Moonen
Gustave
G
Rigo
Jean-Michel
JM
Belachew
Shibeshih
S
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D000077546:Roscovitine
D001552:Benzazepines; D007211:Indoles; D011687:Purines; C120793:alsterpaullone; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases