Effects of Ara-C on neutral sphingomyelinase and mitogen- and stress-activated protein kinases in T-lymphocyte cell lines |
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Authors: | CD Bradshaw KM Ella AL Thomas C Qi KE Meier |
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Affiliation: | Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA. |
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Abstract: | Neutral sphingomyelinase (SMase) can be activated by extracellular signals to produce ceramide, which may affect mitogen-activated protein kinase (MAPK) activities. Neutral SMase activity was assessed in membranes from Jurkat, a human T-cell line, and EL4, a murine T-cell line. Ara-C activated SMase with 10 minutes in both Jurkat and EL4 cells, while phorbol ester (PMA) had no effect. PMA, but not Ara-C or ceramides, activated ERK MAPKS, in Jurkat and EL4. PMA acted synergistically with ionomycin to activate JNK MAPKs in Jurkat and EL4 within 10 minutes. Ara-C activated JNKs only after prolonged incubation (90-120 minutes). Thus, ceramide is not a positive signal for ERK activation in T-cell lines. The effects of Ara-C on JNK activity may be mediated through secondary response pathways. |
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