دورية
Cathepsin B mediates tumor necrosis factor-induced arachidonic acid release in tumor cells.
| العنوان: | Cathepsin B mediates tumor necrosis factor-induced arachidonic acid release in tumor cells. |
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| المؤلفون: | Foghsgaard, Lasse, Lademann, Ulrik, Wissing, Dorte, Poulsen, Birgit, Jaattela, Marja |
| المصدر: | Journal of Biological Chemistry; October 2002, Vol. 277 Issue: 42 p39499-506, 8p |
| مستخلص: | Arachidonic acid (AA) generated by cytosolic phospholipase A2 (cPLA2) has been suggested to function as a second messenger in tumor necrosis factor (TNF)-induced death signaling. Here, we show that cathepsin B-like proteases are required for the TNF-induced AA release in transformed cells. Pharmaceutical inhibitors of cathepsin B blocked TNF-induced AA release in human breast (MCF-7S1) and cervix (ME-180as) carcinoma as well as murine fibrosarcoma (WEHI-S) cells. Furthermore, TNF-induced AA release was significantly reduced in cathepsin B-deficient immortalized murine embryonic fibroblasts. Employing cPLA2-deficient MCF-7S1 cells expressing ectopic cPLA2 or cPLA2-deficient immortalized murine embryonic fibroblasts, we showed that cPLA2 is dispensable for TNF-induced AA release and death in these cells. Furthermore, TNF-induced cathepsin B-dependent AA release could be dissociated from the cathepsin B-independent cell death in MCF-7S1 cells, whereas both events required cathepsin B activity in other cell lines tested. These data suggest that cathepsin B inhibitors may prove useful not only in the direct control of cell death but also in limiting the damage-associated inflammation. |
| قاعدة البيانات: | Supplemental Index |
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