ADRIAMYCIN ACTIVATES C-JUN N-TERMINAL KINASE IN HUMAN LEUKEMIA-CELLS - A RELEVANCE TO APOPTOSIS

We studied the activation of c-jun N-terminal kinase 1 (JNK1) and extr acellular signal-regulated kinases 1 and 2 (ERK 1/2) of mitogen-activa ted protein kinase (MAPK) family by adriamycin (ADR) in the human T ce ll leukemia line, H9. ADR caused an elevation of JNK1 activity at subl ethal or lethal concentrations; however, at lower doses, ADR did not a ctivate JNK1. The induction of JNK1 peaked at 4 h of treatment (about ten-fold over the control), and was sustained up to 5 h posttreatment. This induction preceded the onset of apoptosis, as determined by morp hological features and internucleosomal degradation of DNA. Upon treat ment of cells with JNK1-inducing doses, ADR caused an elevation of ste ady-state levels of c-jun and ATF3 mRNAs, as measured by RT-PCR. In co ntrast, the activity of ERK 1/2 remained unchanged throughout the trea tments, indicating that members of MAPK family are differentially regu lated in ADR-treated cells. A possible role of JNK1 activation in ADR- induced apoptosis is discussed.