Cyclin C and cyclin dependent kinases 1, 2 and 3 in thrombin-induced neuronal cell cycle progression and apoptosis.
The extent to which neurons proceed into the cell cycle and the mechanisms whereby cell cycle re-entry leads to apoptosis vary in response to agonists. We previously showed upregulation of early G1 regulators in thrombin-treated neurons yet neurons did not proceed to S phase but to apoptosis. The objective of this study is to explore mechanisms which might prevent S phase entry and promote apoptosis in thrombin-treated neurons. Cultured rat brain neurons are exposed to thrombin (200nM) for 30min to 4.5h and the expression of cyclin C, cyclin dependent kinases (cdk1, cdk2, cdk3, cdk8) and the cell cycle inhibitor p27 assessed. Our data show a simultaneous decrease of both cyclin C and cdk3 proteins soon after thrombin treatment. The decrease in cyclin C also correlates with decreases in cdk1 and cdk2, at both mRNA and protein levels. There is no change in expression of cdk8 or the cell cycle inhibitor p27 in response to thrombin treatment. These results suggest that decreases in G1-S regulators cyclin C and cdks 3, cdk2 and cdk1 in response to thrombin could make conditions unfavorable for S phase entry and favor neuronal apoptosis.
Rao
Haripriya Vittal
HV
Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street Stop 9424, Lubbock, TX 79430, USA.
Thirumangalakudi
Lakshmi
L
Grammas
Paula
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D056745:Cyclin C; D051357:Cyclin-Dependent Kinase 2 / Q000187:drug effects / Q000378:metabolism; D056849:Cyclin-Dependent Kinase 3; D056850:Cyclin-Dependent Kinase 8; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000187:drug effects / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*
C503676:Ccnc protein, rat; D018797:Cell Cycle Proteins; D056745:Cyclin C; D016213:Cyclins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; C495892:Cdk2 protein, rat; C490914:Cdk3 protein, mouse; C524803:Cdk8 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D056849:Cyclin-Dependent Kinase 3; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D013917:Thrombin