Implication of tyrosine kinases and protein kinase C in dimethyl sulfoxide-induced apoptosis.
We have previously shown that the chemical agent of myeloid differentiation, dimethyl sulfoxide (DMSO), causes apoptosis in human leukemic U937 cells (Château et al. Anal. Cell. Pathol. 1996;10:75-84). Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) led to inhibition of the DMSO-induced apoptosis, suggesting that PKC helps regulate this mechanism by preventing cell death. However, specific inhibitors of PKC (bisindolylmaleimide, D sphingosine), neither triggered apoptosis themselves, nor affected the DMSO-induced apoptosis. Surprisingly, herbimycin A, a potent inhibitor of tyrosine kinases, did not trigger apoptosis itself, but it did prevent DMSO-induced nuclear fragmentation, whereas okadaic acid, an inhibitor of protein phosphatases, triggered apoptosis in U937 cells. These results suggest that DMSO-induced apoptosis requires the activation of an unidentified tyrosine kinase that is probably down-regulated by PKC activation.
Ginestier-Verne
C
C
Laboratoire de Biologie cellulaire et Cytogénétique moléculaire (UPRES-JE 1952), Faculté de Médecine, Université Montpellier I, Nimes, France.
Château
M T
MT
Bureau
J P
JP
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide