Cell membrane changes of structure and function in protein kinase inhibitor-induced polyploid cells.
Exogenous cyclic AMP has been thought to be a chemical without marked pharmacological effect until now, as it is not capable of penetrating the cell membrane in most eucaryotic cells. The present study obtained results consistent with those of most previous studies, showing that exogenous cyclic AMP itself did not interfere with the cell cycle even at the high dose of 100 microM. However, it was found that K252a, a potent inhibitor of protein kinases including protein kinase C, induced DNA re-replication, i.e. DNA synthesis at a elevated DNA ploidy in cells that had not undergone cytokinesis (leading to polyploidization), and that exogenous cyclic AMP markedly potentiated the K252a-induced polyploidization at a very low dose similar to the effective dose of membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP. These findings suggested that the cell membrane changed during the formation of polyploid cells. This supposition was confirmed by scanning electron microscopy to observe structural changes and by determination of cellular attachment to investigate functional changes.
Zong
Z
Z
Division of Basic Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan. zong3961@kanazawa-med.ac.jp
Fujikawa-Yamamoto
K
K
Li
A
A
Yamaguchi
N
N
Chang
Y G
YG
Murakami
M
M
Tanino
M
M
Odashima
S
S
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D000242:Cyclic AMP / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D026121:Indole Alkaloids; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011123:Polyploidy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D003994:Bucladesine; D004247:DNA; C049985:staurosporine aglycone; D000242:Cyclic AMP; D011493:Protein Kinase C