Participation of the Ca(2+)-calmodulin-activated Kinase II in the control of metaphase-anaphase transition in human cells.
Treatment of HeLa S3 cells growing in suspension, and of endothelial cells ECV 304 growing as a monolayer, with the inhibitor of the Ca(2+)-calmodulin activated Kinase II KN-93, blocks cells at metaphase for 15 min (HeLa cells) and 30 min (ECV cells). Thereafter cells resume mitosis and enter anaphase. The inactive isomer KN-92 does not show such effects. The results show the involvement of the CaM K II system in the regulation of the metaphase-anaphase transition whereby the activation of the Kinase II, in particular by calmodulin appears to be affected, the residual autophosphorylation of the CaM K II system apparently sufficing after 15 to 30 min to release the cells into anaphase. The results are compared with the metaphase-blocking effects of the noble gas xenon, where the xenon-induced block can be overcome by small intracellular increases of Ca(2+), thus indicating the CaM K II system as a possible target for xenon.
Petzelt
C P
CP
Experimental Anesthesiology, Department of Anesthesiology and Intensive Care, University Hospital Charité, Humboldt-University, Spandauer Damm 130, Berlin, D-14050, Germany. christian.petzelt@charite.de
Kodirov
S
S
Taschenberger
G
G
Kox
W J
WJ
D000705:Anaphase / Q000502:physiology*; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000502:physiology*; D010766:Phosphorylation; D013449:Sulfonamides / Q000494:pharmacology; D014978:Xenon / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D014978:Xenon; C072105:KN 93; D000096926:Benzenesulfonamides