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Calpeptin suppresses tumor necrosis factor-α-induced death and accumulation of p53 in L929 mouse sarcoma cells

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Abstract

The cytokine tumor necrosis factor (TNF)α induces caspase-dependent cell death in a subset of tumor cells. In this report, we show a novel suppressive effect of calpeptin, a calpain inhibitor, on TNFα-induced cell death and accumulation of p53 in L929 mouse fibrosarcoma. Exposure to 10 ng/ml TNFα induced cell death in >50% of L929 cells within 12 h and stimulated accumulation of p53 (8-fold). Preincubation of cells with calpeptin blocked both TNFα-induced cell death and accumulation of p53 as examined with Western blot. TNFα-induced accumulation of p53 was in part contributed by increase of p53 mRNA level (2.2-fold) in a calpeptin-insensitive manner. Interestingly, other calpain inhibitors tested did not show these effects like calpeptin and TNFα treatment did not increase apparent calpain activity in L929 cells, suggesting that calpeptin may have another function besides targeting calpain. Expression of dominant negative mutant p53Val135 reduced the incidence of TNFα-mediated cell death. Taken together, our findings suggest that TNFα induces calpeptin-dependent, but calpain-independent accumulation of p53 protein as a necessary step leading to death in L929 cells.

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  1. Department of Life Science, Kwangju Institute of Science and Technology, 1 Oryong-dong Puk-gu, Kwangju, 500-712, Korea

    B. J. Kim & Y. K. Jung

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  1. B. J. Kim
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Kim, B.J., Jung, Y.K. Calpeptin suppresses tumor necrosis factor-α-induced death and accumulation of p53 in L929 mouse sarcoma cells. Apoptosis 7, 115–121 (2002). https://doi.org/10.1023/A:1014354229159

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